Neuropsychopharmacology
Encyclopedia
Neuropsychopharmacology (from Greek
, neuron, "nerve"; , psyche, "mind", "soul"; , pharmakon, "poison in classic Greek; drug in modern Greek" and the suffix , -logia, "study of") is an interdisciplinary science related to psychopharmacology
(how drugs affect the mind) and fundamental neuroscience
. It entails research of mechanisms of neuropathology
, pharmacodynamics (drug action)
, psychiatric illness
, and states of consciousness
. These studies are instigated at the detailed level involving neurotransmission
/receptor
activity, bio-chemical
processes, and neural
circuitry. Neuropsychopharmacology supersedes psychopharmacology
in the areas of "how" and "why", and additionally addresses other issues of brain function. Accordingly, the clinical aspect of the field includes psychiatric (psychoactive) as well as neurologic (non-psychoactive) pharmacology-based treatments.
Developments in neuropsychopharmacology may directly impact the studies of anxiety disorder
s, affective disorders, psychotic disorders, degenerative disorder
s, eating behavior
, and sleep behavior
.
The rigorous way fundamental processes of the brain are being discovered is creating a field on par with other “hard sciences” such as chemistry, biology, and physics, so that eventually it may be possible to repair mental illness with ultimate precision. An analogy can be drawn between the brain and an electronic device: neuropsychopharmacology is tantamount to revealing not only the schematic
diagram, but the individual components, and every principle of their operation. The bank of amassed detail and complexity involved is huge; mere samples of some of the details are given in this article.
This account hangs on the assumption that materialism
, the view that all mental states are reducible to brain states, is true.
, alcohol
, and certain plants have been used for millennia by humans to ease suffering or change awareness, but until the modern scientific era nobody knew how these substances worked. The first half of the 20th century saw psychology
and psychiatry
as largely phenomenological
, in that behaviors or themes which were observed in patients could often be correlated to a limited variety of factors such as childhood experience, inherited tendencies, or injury to specific brain areas. Models of mental function and dysfunction were based on such observations. Indeed, the behavioral
branch of psychology dispensed altogether with what actually happened inside the brain, regarding most mental dysfunction as what could be dubbed as "software" errors. In the same era, the nervous system was progressively being studied at the microscopic and chemical level, but there was virtually no mutual benefit with clinical fields - until several developments after World War II
began to bring them together. Neuropsychopharmacology may be regarded to have begun in the earlier 1950s with the discovery of drugs such as MAO inhibitors
, tricyclic antidepressant
s, thorazine and lithium which showed some clinical specificity for mental illnesses such as depression and schizophrenia. Until that time, treatments that actually targeted these complex illnesses were practically non-existent. The prominent methods which could directly affect brain circuitry and neurotransmitter levels were the pre-frontal lobotomy
, and electroconvulsive therapy
, the latter of which was conducted without muscle relaxants which often caused the patient great physical injury.
The field now known as neuropsychopharmacology has resulted from the growth and extension of many previously isolated fields which have met at the core of psychiatric medicine, and engages a broad range of professionals from psychiatrists to researchers in genetics and chemistry. The use of the term has gained popularity since 1990 with the founding of several journals and institutions such as the Hungarian College of Neuropsychopharmacology. This rapidly maturing field shows some degree of flux, as research hypotheses are often restructured based on new information.
, including both normal and drug-induced altered states, and diseases involving mental or cognitive dysfunction
, have a neuro-chemical
basis at the fundamental level, and certain circuit pathways in the central nervous system
at a higher level. (See also: Neuron doctrine
) Thus the understanding of nerve cells or neuron
s in the brain is central to understanding the mind. It is reasoned that the mechanisms involved can be elucidated through modern clinical
and research methods such as genetic manipulation
in animal subjects, imaging techniques such as functional magnetic resonance imaging (fMRI
), and in vitro
studies using selective binding agents on live tissue cultures. These allow neural activity to be monitored and measured in response to a variety of test conditions. Other important observational tools include radiological imaging such as positron emission tomography (PET
) and single-photon emission computed tomography (SPECT
). These imaging techniques are extremely sensitive and can image tiny molecular concentrations on the order of 10−10 M such as found with extrastriatal D1 receptor for dopamine.
One of the ultimate goals is to devise and develop prescriptions of treatment for a variety of neuro-pathological
conditions and psychiatric disorders. More profoundly, though, the knowledge gained may provide insight into the very nature of human thought, mental abilities like learning and memory, and perhaps consciousness itself. A direct product of neuropsychopharmacological research is the knowledge base required to develop drugs
which act on very specific receptors within a neurotransmitter system. These "hyperselective-action" drugs would allow the direct targeting of specific sites of relevant neural activity, thereby maximizing the efficacy
(or technically the potency) of the drug within the clinical target and minimizing adverse effects
.
The groundwork is currently being paved for the next generation of pharmacological
treatments which will improve quality of life with increasing efficiency. For example, contrary to previous thought, it is now known that the adult brain does to some extent grow new neuron
s - the study of which, in addition to neurotrophic factors
, may hold hope for neuro-degenerative diseases like Alzheimer's, Parkinson's, ALS
, and types of chorea
. All of the proteins involved in neurotransmission are a small fraction of the more than 100,000 proteins in the brain. Thus there are many proteins which are not even in the direct path of signal transduction
, any of which may still be a target for specific therapy. At present, novel pharmacological approaches to diseases or conditions are reported at a rate of almost one per week.
may affect the firing of as many as a thousand other neurons in a process called neurotransmission. In this way signals are generated and carried through networks of neurons, the bulk electrical effect of which can be measured directly on the scalp by an EEG
device.
By the last decade of the 20th century, the essential knowledge of all the central features of neurotransmission had been gained . These features are:
The more recent advances involve understanding at the organic
molecular level; biochemical action of the endogenous
ligands
, enzyme
s, receptor proteins, etc. The critical changes affecting cell firing occur when the signalling neurotransmitters from one neuron, acting as ligands, bind to receptors of another neuron. Many neurotransmitter systems and receptors are well known, and research continues toward the identification and characterization of a large number of very specific sub-types of receptors. For the six more important neurotransmitters Glu, GABA, Ach, NE, DA, and 5HT (listed at neurotransmitter
) there are at least 29 major subtypes of receptor. Further "sub-subtypes" exist together with variants, totalling in the hundreds for just these 6 transmitters. - (see serotonin receptor
for example.) It is often found that receptor subtypes have differentiated function, which in principle opens up the possibility of refined intentional control over brain function.
It has previously been known that ultimate control over the membrane voltage or potential of a nerve cell, and thus the firing of the cell, resides with the trans-membrane ion channel
s which control the membrane currents via the ions K
+, Na
+, and Ca
++, and of lesser importance Mg
++ and Cl-. The concentration differences between the inside and outside of the cell determine the membrane voltage.
Precisely how these currents are controlled has become much clearer with the advances in receptor structure and G-protein-coupled
processes. Many receptors are found to be pentameric clusters of five trans-membrane proteins (not necessarily the same) or receptor subunits, each a chain of many amino acids. Transmitters typically bind at the junction between two of these proteins, on the parts that protrude from the cell membrane. If the receptor is of the ionotropic type, a central pore or channel in the middle of the proteins will be mechanically moved to allow certain ions to flow through, thus altering the ion concentration difference. If the receptor is of the metabotropic type, G-proteins will cause metabolism inside the cell that may eventually change other ion channels. Researchers are better understanding precisely how these changes occur based on the protein structure shapes and chemical properties.
The scope of this activity has been stretched even further to the very blueprint of life since the clarification of the mechanism underlying gene transcription
. The synthesis
of cellular proteins from nuclear DNA
has the same fundamental machinery for all cells; the exploration of which now has a firm basis thanks to the Human Genome Project
which has enumerated the entire human DNA sequence, although many of the estimated 35,000 genes remain to be identified. The complete neurotransmission process extends to the genetic level. Gene expression
determines protein structures through type II RNA polymerase
. So enzymes which synthesize or breakdown neurotransmitters, receptors, and ion channels are each made from mRNA via the DNA transcription of their respective gene or genes. But neurotransmission, in addition to controlling ion channels either directly or otherwise through metabotropic processes, also actually modulates gene expression. This is most prominently achieved through modification of the transcription initiation process by a variety of transcription factors produced from receptor activity.
Aside from the important pharmacological possibilities of gene expression pathways, the correspondence of a gene with its protein allows the important analytical tool of gene knockout
. Living specimens can be created using homolog recombination in which a specific gene cannot be expressed. The organism will then be deficient in the associated protein which may be a specific receptor. This method avoids chemical blockade which can produce confusing or ambiguous secondary effects so that the effects of a lack of receptor can be studied in a purer sense.
") and safe to consume. The 2005 Physicians' Desk Reference
lists twice the number of prescription drug
s as the 1990 version. Many people by now are familiar with "selective serotonin reuptake inhibitor
s", or SSRIs which exemplify modern pharmaceuticals
. These SSRI anti-depressant
drugs, such as Paxil and Prozac, selectively and therefore primarily inhibit the transport of serotonin which prolongs the activity in the synapse. There are numerous categories of selective drugs, and transport blockage is only one mode of action. The FDA
has approved drugs which selectively act on each of the major neurotransmitters such as NE
reuptake inhibitor antidepressants, DA
blocker anti-psychotics
, and GABA
agonist
tranquilizer
s (benzodiazepine
s).
New endogenous chemicals are continually identified. Specific receptors have been found for the drugs THC
(cannabis) and GHB
, with endogenous transmitters anandamide and GHB. Another recent major discovery occurred in 1999 when orexin
, or hypocretin, was found to have a role in arousal, since the lack of orexin receptors mirrors the condition of narcolepsy
. Orexin agonism may explain the anti-narcoleptic action of the drug modafinil
which was already being used only a year prior.
The next step, which major pharmaceutical companies
are currently working hard to develop, are receptor subtype-specific drugs and other specific agents. An example is the push for better anti-anxiety agents (anxiolytic
s) based on GABAA(α2) agonists, CRF
1 blockers, and 5HT2c blockers. Another is the proposal of new routes of exploration for anti-psychotics such as glycine reuptake inhibitors. Although the capabilities exist for receptor-specific drugs, a shortcoming of drug therapy is the lack of ability to provide anatomical specificity. By altering receptor function in one part of the brain, abnormal activity can be induced in other parts of the brain due to the same type of receptor changes. A common example is the effect of D2 altering drugs (neuroleptics) which can help schizophrenia, but cause a variety of dyskinesia
s by their action on motor cortex.
Modern studies are revealing details of mechanisms of damage to the nervous system such as apoptosis
(programmed cell death) and free-radical
disruption. PCP has been found to cause cell death in striatopallidal cells and abnormal vacuolization
in hippocampal
and other neurons. The hallucinogen persisting perception disorder
(HPPD), also known as post-psychedelic perception disorder, has been observed in patients as long as 26 years after LSD use. The plausible cause of HPPD is damage to the inhibitory GABA circuit in the visual pathway (GABA agonists such as midazolam can decrease some effects of LSD intoxication). The damage may be the result of an excitotoxic
response of 5HT2 interneuron
s. [Note: the vast majority of LSD users do not experience HPPD. Its manifestation may be equally dependent on individual brain chemistry as on the drug use itself] As for MDMA, aside from persistent losses of 5HT and SERT
, long-lasting reduction of serotonergic axon
s and terminals is found from short-term use, and regrowth may be of compromised function.
). The signal paths of neurons are hyper-organized beyond the cellular scale into often complex neural circuit pathways. Knowledge of these pathways is perhaps the easiest to interpret, being most recognizable from a systems analysis point of view, as may been seen in the following abstracts.
Progress has been made on central mechanisms of hallucination
believed to be common to psychedelic drug
s and psychotic illness
. It is likely the effect of partial agonistic action on the serotonin system. The 5HT2A receptor and possibly the 5HT1C are involved by releasing glutamate in the frontal cortex
, while simultaneously in the locus coeruleus sensory information is promoted and spontaneous activity decreases. One hypothesis suggests that in the frontal cortex, 5HT2A promotes late asynchronous excitatory post-synaptic potentials
, a process antagonized by serotonin itself through 5HT1 which may explain why SSRI's and other serotonin-affecting drugs do not normally cause a patient to hallucinate.
Circadian rhythm
, or sleep/wake cycling, is centered in the suprachiasmatic nucleus
(SCN) within the hypothalamus, and is marked by melatonin
levels 2000-4,000% higher during sleep than in the day. A circuit is known to start with melanopsin
cells in the eye which stimulate the SCN through glutamate neurons of the hypothalamic tract. GABA-ergic neurons from the SCN inhibit the paraventricular nucleus
, which signals the superior cervical ganglion (SCG) through sympathetic
fibers. The output of the SCG, stimulates NE receptors (β
) in the pineal gland
which produces N-acetyltransferase, causing production of melatonin from serotonin. Inhibitory melatonin receptors in the SCN then provide a positive feedback pathway
. Therefore, light inhibits the production of melatonin which "entrains
" the 24-hour cycle of SCN activity,. The SCN also receives signals from other parts of the brain, and its (approximately) 24 hour cycle does not only depend on light patterns. In fact, sectioned tissue from the SCN will exhibit daily cycle in vitro for many days. Additionally, (not shown in diagram), the basal nucleus provides GABA-ergic inhibitory input to the pre-optic anterior hypothalamus (PAH). When adenosine builds up from the metabolism of ATP throughout the day, it binds to adenosine receptors, inhibiting the basal nucleus. The PAH is then activated, generating slow-wave sleep activity. Caffeine
is known to block adenosine receptors, thereby inhibiting sleep among other things.
The ECNP publishes European Neuropsychopharmacology, and as part of the Reed Elsevier Group, the ACNP publishes the journal Neuropsychopharmacology
, and the CINP publishes the journal International Journal of Neuropsychopharmacology with Cambridge University Press
.
In 2002 the most recent comprehensive collected work of the ACNP, "Neuropsychopharmacology: The Fifth Generation of Progress" was compiled. It is one measure of the current state of knowledge, and might be said to represent a landmark in the century-long goal to establish the basic neuro-biological principles which govern the actions of the brain.
Many other journals exist which contain relevant information such as Neuroscience
.
Some of them are listed at Brown University Library.
Ancient Greek
Ancient Greek is the stage of the Greek language in the periods spanning the times c. 9th–6th centuries BC, , c. 5th–4th centuries BC , and the c. 3rd century BC – 6th century AD of ancient Greece and the ancient world; being predated in the 2nd millennium BC by Mycenaean Greek...
, neuron, "nerve"; , psyche, "mind", "soul"; , pharmakon, "poison in classic Greek; drug in modern Greek" and the suffix , -logia, "study of") is an interdisciplinary science related to psychopharmacology
Psychopharmacology
Psychopharmacology is the scientific study of the actions of drugs and their effects on mood, sensation, thinking, and behavior...
(how drugs affect the mind) and fundamental neuroscience
Neuroscience
Neuroscience is the scientific study of the nervous system. Traditionally, neuroscience has been seen as a branch of biology. However, it is currently an interdisciplinary science that collaborates with other fields such as chemistry, computer science, engineering, linguistics, mathematics,...
. It entails research of mechanisms of neuropathology
Neuropathology
Neuropathology is the study of disease of nervous system tissue, usually in the form of either small surgical biopsies or whole autopsy brains. Neuropathology is a subspecialty of anatomic pathology, neurology, and neurosurgery...
, pharmacodynamics (drug action)
Pharmacodynamics
Pharmacodynamics is the study of the biochemical and physiological effects of drugs on the body or on microorganisms or parasites within or on the body and the mechanisms of drug action and the relationship between drug concentration and effect...
, psychiatric illness
Mental illness
A mental disorder or mental illness is a psychological or behavioral pattern generally associated with subjective distress or disability that occurs in an individual, and which is not a part of normal development or culture. Such a disorder may consist of a combination of affective, behavioural,...
, and states of consciousness
Consciousness
Consciousness is a term that refers to the relationship between the mind and the world with which it interacts. It has been defined as: subjectivity, awareness, the ability to experience or to feel, wakefulness, having a sense of selfhood, and the executive control system of the mind...
. These studies are instigated at the detailed level involving neurotransmission
Neurotransmission
Neurotransmission , also called synaptic transmission, is the process by which signaling molecules called neurotransmitters are released by a neuron , and bind to and activate the receptors of another neuron...
/receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
activity, bio-chemical
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...
processes, and neural
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...
circuitry. Neuropsychopharmacology supersedes psychopharmacology
Psychopharmacology
Psychopharmacology is the scientific study of the actions of drugs and their effects on mood, sensation, thinking, and behavior...
in the areas of "how" and "why", and additionally addresses other issues of brain function. Accordingly, the clinical aspect of the field includes psychiatric (psychoactive) as well as neurologic (non-psychoactive) pharmacology-based treatments.
Developments in neuropsychopharmacology may directly impact the studies of anxiety disorder
Anxiety disorder
Anxiety disorder is a blanket term covering several different forms of abnormal and pathological fear and anxiety. Conditions now considered anxiety disorders only came under the aegis of psychiatry at the end of the 19th century. Gelder, Mayou & Geddes explains that anxiety disorders are...
s, affective disorders, psychotic disorders, degenerative disorder
Degenerative disease
A degenerative disease, also called neurodegenerative disease, is a disease in which the function or structure of the affected tissues or organs will progressively deteriorate over time, whether due to normal bodily wear or lifestyle choices such as exercise or eating habits...
s, eating behavior
Eating disorder
Eating disorders refer to a group of conditions defined by abnormal eating habits that may involve either insufficient or excessive food intake to the detriment of an individual's physical and mental health. Bulimia nervosa, anorexia nervosa, and binge eating disorder are the most common specific...
, and sleep behavior
Sleep
Sleep is a naturally recurring state characterized by reduced or absent consciousness, relatively suspended sensory activity, and inactivity of nearly all voluntary muscles. It is distinguished from quiet wakefulness by a decreased ability to react to stimuli, and is more easily reversible than...
.
The rigorous way fundamental processes of the brain are being discovered is creating a field on par with other “hard sciences” such as chemistry, biology, and physics, so that eventually it may be possible to repair mental illness with ultimate precision. An analogy can be drawn between the brain and an electronic device: neuropsychopharmacology is tantamount to revealing not only the schematic
Schematic
A schematic diagram represents the elements of a system using abstract, graphic symbols rather than realistic pictures. A schematic usually omits all details that are not relevant to the information the schematic is intended to convey, and may add unrealistic elements that aid comprehension...
diagram, but the individual components, and every principle of their operation. The bank of amassed detail and complexity involved is huge; mere samples of some of the details are given in this article.
This account hangs on the assumption that materialism
Materialism
In philosophy, the theory of materialism holds that the only thing that exists is matter; that all things are composed of material and all phenomena are the result of material interactions. In other words, matter is the only substance...
, the view that all mental states are reducible to brain states, is true.
History
Drugs such as opiumOpium
Opium is the dried latex obtained from the opium poppy . Opium contains up to 12% morphine, an alkaloid, which is frequently processed chemically to produce heroin for the illegal drug trade. The latex also includes codeine and non-narcotic alkaloids such as papaverine, thebaine and noscapine...
, alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
, and certain plants have been used for millennia by humans to ease suffering or change awareness, but until the modern scientific era nobody knew how these substances worked. The first half of the 20th century saw psychology
Psychology
Psychology is the study of the mind and behavior. Its immediate goal is to understand individuals and groups by both establishing general principles and researching specific cases. For many, the ultimate goal of psychology is to benefit society...
and psychiatry
Psychiatry
Psychiatry is the medical specialty devoted to the study and treatment of mental disorders. These mental disorders include various affective, behavioural, cognitive and perceptual abnormalities...
as largely phenomenological
Phenomenology (science)
The term phenomenology in science is used to describe a body of knowledge that relates empirical observations of phenomena to each other, in a way that is consistent with fundamental theory, but is not directly derived from theory. For example, we find the following definition in the Concise...
, in that behaviors or themes which were observed in patients could often be correlated to a limited variety of factors such as childhood experience, inherited tendencies, or injury to specific brain areas. Models of mental function and dysfunction were based on such observations. Indeed, the behavioral
Behaviorism
Behaviorism , also called the learning perspective , is a philosophy of psychology based on the proposition that all things that organisms do—including acting, thinking, and feeling—can and should be regarded as behaviors, and that psychological disorders are best treated by altering behavior...
branch of psychology dispensed altogether with what actually happened inside the brain, regarding most mental dysfunction as what could be dubbed as "software" errors. In the same era, the nervous system was progressively being studied at the microscopic and chemical level, but there was virtually no mutual benefit with clinical fields - until several developments after World War II
World War II
World War II, or the Second World War , was a global conflict lasting from 1939 to 1945, involving most of the world's nations—including all of the great powers—eventually forming two opposing military alliances: the Allies and the Axis...
began to bring them together. Neuropsychopharmacology may be regarded to have begun in the earlier 1950s with the discovery of drugs such as MAO inhibitors
Monoamine oxidase inhibitor
Monoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....
, tricyclic antidepressant
Tricyclic antidepressant
Tricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms...
s, thorazine and lithium which showed some clinical specificity for mental illnesses such as depression and schizophrenia. Until that time, treatments that actually targeted these complex illnesses were practically non-existent. The prominent methods which could directly affect brain circuitry and neurotransmitter levels were the pre-frontal lobotomy
Psychosurgery
Psychosurgery, also called neurosurgery for mental disorder , is the neurosurgical treatment of mental disorder. Psychosurgery has always been a controversial medical field. The modern history of psychosurgery begins in the 1880s under the Swiss psychiatrist Gottlieb Burckhardt...
, and electroconvulsive therapy
Electroconvulsive therapy
Electroconvulsive therapy , formerly known as electroshock, is a psychiatric treatment in which seizures are electrically induced in anesthetized patients for therapeutic effect. Its mode of action is unknown...
, the latter of which was conducted without muscle relaxants which often caused the patient great physical injury.
The field now known as neuropsychopharmacology has resulted from the growth and extension of many previously isolated fields which have met at the core of psychiatric medicine, and engages a broad range of professionals from psychiatrists to researchers in genetics and chemistry. The use of the term has gained popularity since 1990 with the founding of several journals and institutions such as the Hungarian College of Neuropsychopharmacology. This rapidly maturing field shows some degree of flux, as research hypotheses are often restructured based on new information.
Overview
An implicit premise in neuropsychopharmacology with regard to the psychological aspects is that all states of mindMind
The concept of mind is understood in many different ways by many different traditions, ranging from panpsychism and animism to traditional and organized religious views, as well as secular and materialist philosophies. Most agree that minds are constituted by conscious experience and intelligent...
, including both normal and drug-induced altered states, and diseases involving mental or cognitive dysfunction
Abnormality (behavior)
Abnormality, in the vivid sense of something deviating from the normal or differing from the typical , is a subjectively defined behavioral characteristic, assigned to those with rare or dysfunctional conditions...
, have a neuro-chemical
Neurochemistry
Neurochemistry is the specific study of neurochemicals, which include neurotransmitters and other molecules such as neuro-active drugs that influence neuron function. This principle closely examines the manner in which these neurochemicals influence the network of neural operation...
basis at the fundamental level, and certain circuit pathways in the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
at a higher level. (See also: Neuron doctrine
Neuron doctrine
The neuron doctrine is a descriptive term for the fundamental concept that the nervous system is made up of discrete individual cells, a discovery due to decisive neuro-anatomical work of Santiago Ramon y Cajal and later presented, among others, by H. Waldeyer-Hartz...
) Thus the understanding of nerve cells or neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s in the brain is central to understanding the mind. It is reasoned that the mechanisms involved can be elucidated through modern clinical
Clinical psychology
Clinical psychology is an integration of science, theory and clinical knowledge for the purpose of understanding, preventing, and relieving psychologically-based distress or dysfunction and to promote subjective well-being and personal development...
and research methods such as genetic manipulation
Genetic engineering
Genetic engineering, also called genetic modification, is the direct human manipulation of an organism's genome using modern DNA technology. It involves the introduction of foreign DNA or synthetic genes into the organism of interest...
in animal subjects, imaging techniques such as functional magnetic resonance imaging (fMRI
Functional magnetic resonance imaging
Functional magnetic resonance imaging or functional MRI is a type of specialized MRI scan used to measure the hemodynamic response related to neural activity in the brain or spinal cord of humans or other animals. It is one of the most recently developed forms of neuroimaging...
), and in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
studies using selective binding agents on live tissue cultures. These allow neural activity to be monitored and measured in response to a variety of test conditions. Other important observational tools include radiological imaging such as positron emission tomography (PET
Positron emission tomography
Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...
) and single-photon emission computed tomography (SPECT
Single photon emission computed tomography
Single-photon emission computed tomography is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera. However, it is able to provide true 3D information...
). These imaging techniques are extremely sensitive and can image tiny molecular concentrations on the order of 10−10 M such as found with extrastriatal D1 receptor for dopamine.
One of the ultimate goals is to devise and develop prescriptions of treatment for a variety of neuro-pathological
Neuropathology
Neuropathology is the study of disease of nervous system tissue, usually in the form of either small surgical biopsies or whole autopsy brains. Neuropathology is a subspecialty of anatomic pathology, neurology, and neurosurgery...
conditions and psychiatric disorders. More profoundly, though, the knowledge gained may provide insight into the very nature of human thought, mental abilities like learning and memory, and perhaps consciousness itself. A direct product of neuropsychopharmacological research is the knowledge base required to develop drugs
Psychoactive drug
A psychoactive drug, psychopharmaceutical, or psychotropic is a chemical substance that crosses the blood–brain barrier and acts primarily upon the central nervous system where it affects brain function, resulting in changes in perception, mood, consciousness, cognition, and behavior...
which act on very specific receptors within a neurotransmitter system. These "hyperselective-action" drugs would allow the direct targeting of specific sites of relevant neural activity, thereby maximizing the efficacy
Efficacy
Efficacy is the capacity to produce an effect. It has different specific meanings in different fields. In medicine, it is the ability of an intervention or drug to reproduce a desired effect in expert hands and under ideal circumstances.- Healthcare :...
(or technically the potency) of the drug within the clinical target and minimizing adverse effects
Adverse effect (medicine)
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
.
The groundwork is currently being paved for the next generation of pharmacological
Pharmacology
Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...
treatments which will improve quality of life with increasing efficiency. For example, contrary to previous thought, it is now known that the adult brain does to some extent grow new neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s - the study of which, in addition to neurotrophic factors
Neurotrophin
Neurotrophins are a family of proteins that induce the survival, development, and function of neurons.They belong to a class of growth factors, secreted proteins that are capable of signaling particular cells to survive, differentiate, or grow. Growth factors such as neurotrophins that promote the...
, may hold hope for neuro-degenerative diseases like Alzheimer's, Parkinson's, ALS
Motor neurone disease
The motor neurone diseases are a group of neurological disorders that selectively affect motor neurones, the cells that control voluntary muscle activity including speaking, walking, breathing, swallowing and general movement of the body. They are generally progressive in nature, and can cause...
, and types of chorea
Chorea (disease)
Choreia is an abnormal involuntary movement disorder, one of a group of neurological disorders called dyskinesias. The term choreia is derived from the Greek word χορεία , see choreia , as the quick movements of the feet or hands are vaguely comparable to dancing or piano playing.The term...
. All of the proteins involved in neurotransmission are a small fraction of the more than 100,000 proteins in the brain. Thus there are many proteins which are not even in the direct path of signal transduction
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
, any of which may still be a target for specific therapy. At present, novel pharmacological approaches to diseases or conditions are reported at a rate of almost one per week.
Neurotransmission
So far as we know, everything we perceive, feel, think, know, and do are a result of neurons firing and resetting. When a cell in the brain fires, small chemical and electrical swings called the action potentialAction potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...
may affect the firing of as many as a thousand other neurons in a process called neurotransmission. In this way signals are generated and carried through networks of neurons, the bulk electrical effect of which can be measured directly on the scalp by an EEG
Electroencephalography
Electroencephalography is the recording of electrical activity along the scalp. EEG measures voltage fluctuations resulting from ionic current flows within the neurons of the brain...
device.
By the last decade of the 20th century, the essential knowledge of all the central features of neurotransmission had been gained . These features are:
- The synthesisBiosynthesisBiosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...
and storage of neurotransmitterNeurotransmitterNeurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
substances, - The transport of synaptic vesiclesVesicle (biology)A vesicle is a bubble of liquid within another liquid, a supramolecular assembly made up of many different molecules. More technically, a vesicle is a small membrane-enclosed sack that can store or transport substances. Vesicles can form naturally because of the properties of lipid membranes , or...
and subsequent release into the synapseSynapseIn the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
, - ReceptorReceptor (biochemistry)In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
activation and cascadeBiochemical cascadeA biochemical cascade is a series of chemical reactions in which the products of one reaction are consumed in the next reaction. There are several important biochemical cascade reactions in biochemistry, including the enzymatic cascades, such as the coagulation cascade and the complement system,...
function, - TransportMonoamine transporterMonoamine transporters are protein structures that function as integral plasma membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. Three major classes of MATs are responsible for the reuptake of their associated amine neurotransmitters...
mechanisms (reuptake) and/or enzyme degradation
The more recent advances involve understanding at the organic
Organic compound
An organic compound is any member of a large class of gaseous, liquid, or solid chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of carbon-containing compounds such as carbides, carbonates, simple oxides of carbon, and cyanides, as well as the...
molecular level; biochemical action of the endogenous
Endogenous
Endogenous substances are those that originate from within an organism, tissue, or cell. Endogenous retroviruses are caused by ancient infections of germ cells in humans, mammals and other vertebrates...
ligands
Ligand (biochemistry)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...
, enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s, receptor proteins, etc. The critical changes affecting cell firing occur when the signalling neurotransmitters from one neuron, acting as ligands, bind to receptors of another neuron. Many neurotransmitter systems and receptors are well known, and research continues toward the identification and characterization of a large number of very specific sub-types of receptors. For the six more important neurotransmitters Glu, GABA, Ach, NE, DA, and 5HT (listed at neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
) there are at least 29 major subtypes of receptor. Further "sub-subtypes" exist together with variants, totalling in the hundreds for just these 6 transmitters. - (see serotonin receptor
5-HT receptor
The serotonin receptors, also known as 5-hydroxytryptamine receptors or 5-HT receptors, are a group of G protein-coupled receptors and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory neurotransmission...
for example.) It is often found that receptor subtypes have differentiated function, which in principle opens up the possibility of refined intentional control over brain function.
It has previously been known that ultimate control over the membrane voltage or potential of a nerve cell, and thus the firing of the cell, resides with the trans-membrane ion channel
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
s which control the membrane currents via the ions K
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...
+, Na
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
+, and Ca
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
++, and of lesser importance Mg
Magnesium
Magnesium is a chemical element with the symbol Mg, atomic number 12, and common oxidation number +2. It is an alkaline earth metal and the eighth most abundant element in the Earth's crust and ninth in the known universe as a whole...
++ and Cl-. The concentration differences between the inside and outside of the cell determine the membrane voltage.
G protein
G proteins are a family of proteins involved in transmitting chemical signals outside the cell, and causing changes inside the cell. They communicate signals from many hormones, neurotransmitters, and other signaling factors. G protein-coupled receptors are transmembrane receptors...
processes. Many receptors are found to be pentameric clusters of five trans-membrane proteins (not necessarily the same) or receptor subunits, each a chain of many amino acids. Transmitters typically bind at the junction between two of these proteins, on the parts that protrude from the cell membrane. If the receptor is of the ionotropic type, a central pore or channel in the middle of the proteins will be mechanically moved to allow certain ions to flow through, thus altering the ion concentration difference. If the receptor is of the metabotropic type, G-proteins will cause metabolism inside the cell that may eventually change other ion channels. Researchers are better understanding precisely how these changes occur based on the protein structure shapes and chemical properties.
The scope of this activity has been stretched even further to the very blueprint of life since the clarification of the mechanism underlying gene transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
. The synthesis
Protein biosynthesis
Protein biosynthesis is the process in which cells build or manufacture proteins. The term is sometimes used to refer only to protein translation but more often it refers to a multi-step process, beginning with amino acid synthesis and transcription of nuclear DNA into messenger RNA, which is then...
of cellular proteins from nuclear DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
has the same fundamental machinery for all cells; the exploration of which now has a firm basis thanks to the Human Genome Project
Human Genome Project
The Human Genome Project is an international scientific research project with a primary goal of determining the sequence of chemical base pairs which make up DNA, and of identifying and mapping the approximately 20,000–25,000 genes of the human genome from both a physical and functional...
which has enumerated the entire human DNA sequence, although many of the estimated 35,000 genes remain to be identified. The complete neurotransmission process extends to the genetic level. Gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
determines protein structures through type II RNA polymerase
RNA polymerase
RNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...
. So enzymes which synthesize or breakdown neurotransmitters, receptors, and ion channels are each made from mRNA via the DNA transcription of their respective gene or genes. But neurotransmission, in addition to controlling ion channels either directly or otherwise through metabotropic processes, also actually modulates gene expression. This is most prominently achieved through modification of the transcription initiation process by a variety of transcription factors produced from receptor activity.
Aside from the important pharmacological possibilities of gene expression pathways, the correspondence of a gene with its protein allows the important analytical tool of gene knockout
Gene knockout
A gene knockout is a genetic technique in which one of an organism's genes is made inoperative . Also known as knockout organisms or simply knockouts, they are used in learning about a gene that has been sequenced, but which has an unknown or incompletely known function...
. Living specimens can be created using homolog recombination in which a specific gene cannot be expressed. The organism will then be deficient in the associated protein which may be a specific receptor. This method avoids chemical blockade which can produce confusing or ambiguous secondary effects so that the effects of a lack of receptor can be studied in a purer sense.
Drugs
The inception of many classes of drugs is in principle straightforward: any chemical that can enhance or diminish the action of a target protein could be investigated further for such use. The trick is to find such a chemical that is receptor-specific (cf. "dirty drugDirty drug
A dirty drug is an informal term used in pharmacology to describe drugs that may bind to many different molecular targets or receptors in the body, and so tend to have a wide range of effects and possibly negative side effects...
") and safe to consume. The 2005 Physicians' Desk Reference
Physicians' Desk Reference
The Physicians' Desk Reference is a commercially published compilation of manufacturers' prescribing information on prescription drugs, updated annually...
lists twice the number of prescription drug
Prescription drug
A prescription medication is a licensed medicine that is regulated by legislation to require a medical prescription before it can be obtained. The term is used to distinguish it from over-the-counter drugs which can be obtained without a prescription...
s as the 1990 version. Many people by now are familiar with "selective serotonin reuptake inhibitor
Selective serotonin reuptake inhibitor
Selective serotonin re-uptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. The efficacy of SSRIs is disputed...
s", or SSRIs which exemplify modern pharmaceuticals
Pharmacology
Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...
. These SSRI anti-depressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
drugs, such as Paxil and Prozac, selectively and therefore primarily inhibit the transport of serotonin which prolongs the activity in the synapse. There are numerous categories of selective drugs, and transport blockage is only one mode of action. The FDA
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
has approved drugs which selectively act on each of the major neurotransmitters such as NE
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
reuptake inhibitor antidepressants, DA
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
blocker anti-psychotics
Antipsychotic
An antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...
, and GABA
Gamma-aminobutyric acid
γ-Aminobutyric acid is the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays a role in regulating neuronal excitability throughout the nervous system...
agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
tranquilizer
Tranquilizer
A tranquilizer, or tranquilliser , is a drug that induces tranquility in an individual.The term "tranquilizer" is imprecise, and is usually qualified, or replaced with more precise terms:...
s (benzodiazepine
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
s).
New endogenous chemicals are continually identified. Specific receptors have been found for the drugs THC
THC
THC commonly refers to tetrahydrocannabinol, the main active chemical compound in Cannabis.THC may also refer to:* Tan Holdings Corporation...
(cannabis) and GHB
Gamma-Hydroxybutyric acid
γ-Hydroxybutyric acid , also known as 4-hydroxybutanoic acid and sodium oxybate when used for medicinal purposes, is a naturally occurring substance found in the central nervous system, wine, beef, small citrus fruits, and almost all animals in small amounts. It is also categorized as an illegal...
, with endogenous transmitters anandamide and GHB. Another recent major discovery occurred in 1999 when orexin
Orexin
Orexins, also called hypocretins, are the common names given to a pair of excitatory neuropeptide hormones that were simultaneously discovered by two groups of researchers in rat brains....
, or hypocretin, was found to have a role in arousal, since the lack of orexin receptors mirrors the condition of narcolepsy
Narcolepsy
Narcolepsy is a chronic sleep disorder, or dyssomnia, characterized by excessive sleepiness and sleep attacks at inappropriate times, such as while at work. People with narcolepsy often experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which often is confused with insomnia...
. Orexin agonism may explain the anti-narcoleptic action of the drug modafinil
Modafinil
Modafinil is an analeptic drug manufactured by Cephalon, and is approved by the U.S. Food and Drug Administration for the treatment of narcolepsy, shift work sleep disorder, and excessive daytime sleepiness associated with obstructive sleep apnea...
which was already being used only a year prior.
The next step, which major pharmaceutical companies
Pharmaceutical company
The pharmaceutical industry develops, produces, and markets drugs licensed for use as medications. Pharmaceutical companies are allowed to deal in generic and/or brand medications and medical devices...
are currently working hard to develop, are receptor subtype-specific drugs and other specific agents. An example is the push for better anti-anxiety agents (anxiolytic
Anxiolytic
An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
s) based on GABAA(α2) agonists, CRF
Corticotropin-releasing hormone
Corticotropin-releasing hormone , originally named corticotropin-releasing factor , and also called corticoliberin, is a polypeptide hormone and neurotransmitter involved in the stress response...
1 blockers, and 5HT2c blockers. Another is the proposal of new routes of exploration for anti-psychotics such as glycine reuptake inhibitors. Although the capabilities exist for receptor-specific drugs, a shortcoming of drug therapy is the lack of ability to provide anatomical specificity. By altering receptor function in one part of the brain, abnormal activity can be induced in other parts of the brain due to the same type of receptor changes. A common example is the effect of D2 altering drugs (neuroleptics) which can help schizophrenia, but cause a variety of dyskinesia
Dyskinesia
Dyskinesia is a movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements, similar to tics or choreia. Dyskinesia can be anything from a slight tremor of the hands to uncontrollable movement of, most commonly, the upper body but...
s by their action on motor cortex.
Modern studies are revealing details of mechanisms of damage to the nervous system such as apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
(programmed cell death) and free-radical
Radical (chemistry)
Radicals are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative, or zero charge...
disruption. PCP has been found to cause cell death in striatopallidal cells and abnormal vacuolization
Vacuole
A vacuole is a membrane-bound organelle which is present in all plant and fungal cells and some protist, animal and bacterial cells. Vacuoles are essentially enclosed compartments which are filled with water containing inorganic and organic molecules including enzymes in solution, though in certain...
in hippocampal
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
and other neurons. The hallucinogen persisting perception disorder
Hallucinogen persisting perception disorder
Hallucinogen persisting perception disorder is a disorder characterized by a continual presence of visual disturbances that are reminiscent of those generated by the ingestion of hallucinogenic substances. Previous use of hallucinogens by the person is needed, though not sufficient, for...
(HPPD), also known as post-psychedelic perception disorder, has been observed in patients as long as 26 years after LSD use. The plausible cause of HPPD is damage to the inhibitory GABA circuit in the visual pathway (GABA agonists such as midazolam can decrease some effects of LSD intoxication). The damage may be the result of an excitotoxic
Excitotoxicity
Excitotoxicity is the pathological process by which nerve cells are damaged and killed by excessive stimulation by neurotransmitters such as glutamate and similar substances. This occurs when receptors for the excitatory neurotransmitter glutamate such as the NMDA receptor and AMPA receptor are...
response of 5HT2 interneuron
Interneuron
An interneuron is a multipolar neuron which connects afferent neurons and efferent neurons in neural pathways...
s. [Note: the vast majority of LSD users do not experience HPPD. Its manifestation may be equally dependent on individual brain chemistry as on the drug use itself] As for MDMA, aside from persistent losses of 5HT and SERT
Serotonin transporter
The serotonin transporter is a monoamine transporter protein.This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it...
, long-lasting reduction of serotonergic axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
s and terminals is found from short-term use, and regrowth may be of compromised function.
Neural circuits
It is a not-so-recent discovery that many functions of the brain are localized to associated areas like motor and speech ability. Functional associations of brain anatomy are now being complemented with clinical, behavioral, and genetic correlates of receptor action, completing the knowledge of neural signalling (see also: Human Cognome ProjectHuman Cognome Project
The Human Cognome Project is an effort to reverse engineer the human brain by studying both its structure and function, in order to fully understand mental processes, also known as cognition. The project has many parallels to the Human Genome Project...
). The signal paths of neurons are hyper-organized beyond the cellular scale into often complex neural circuit pathways. Knowledge of these pathways is perhaps the easiest to interpret, being most recognizable from a systems analysis point of view, as may been seen in the following abstracts.
Progress has been made on central mechanisms of hallucination
Hallucination
A hallucination, in the broadest sense of the word, is a perception in the absence of a stimulus. In a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid,...
believed to be common to psychedelic drug
Psychedelic drug
A psychedelic substance is a psychoactive drug whose primary action is to alter cognition and perception. Psychedelics are part of a wider class of psychoactive drugs known as hallucinogens, a class that also includes related substances such as dissociatives and deliriants...
s and psychotic illness
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
. It is likely the effect of partial agonistic action on the serotonin system. The 5HT2A receptor and possibly the 5HT1C are involved by releasing glutamate in the frontal cortex
Frontal lobe
The frontal lobe is an area in the brain of humans and other mammals, located at the front of each cerebral hemisphere and positioned anterior to the parietal lobe and superior and anterior to the temporal lobes...
, while simultaneously in the locus coeruleus sensory information is promoted and spontaneous activity decreases. One hypothesis suggests that in the frontal cortex, 5HT2A promotes late asynchronous excitatory post-synaptic potentials
Excitatory postsynaptic potential
In neuroscience, an excitatory postsynaptic potential is a temporary depolarization of postsynaptic membrane potential caused by the flow of positively charged ions into the postsynaptic cell as a result of opening of ligand-sensitive channels...
, a process antagonized by serotonin itself through 5HT1 which may explain why SSRI's and other serotonin-affecting drugs do not normally cause a patient to hallucinate.
Circadian rhythm
A circadian rhythm, popularly referred to as body clock, is an endogenously driven , roughly 24-hour cycle in biochemical, physiological, or behavioural processes. Circadian rhythms have been widely observed in plants, animals, fungi and cyanobacteria...
, or sleep/wake cycling, is centered in the suprachiasmatic nucleus
Suprachiasmatic nucleus
The suprachiasmatic nucleus or nuclei, abbreviated SCN, is a tiny region on the brain's midline, situated directly above the optic chiasm. It is responsible for controlling circadian rhythms...
(SCN) within the hypothalamus, and is marked by melatonin
Melatonin
Melatonin , also known chemically as N-acetyl-5-methoxytryptamine, is a naturally occurring compound found in animals, plants, and microbes...
levels 2000-4,000% higher during sleep than in the day. A circuit is known to start with melanopsin
Melanopsin
Melanopsin is a photopigment found in specialized photosensitive ganglion cells of the retina that are involved in the regulation of circadian rhythms, pupillary light reflex, and other non-visual responses to light. In structure, melanopsin is an opsin, a retinylidene protein variety of...
cells in the eye which stimulate the SCN through glutamate neurons of the hypothalamic tract. GABA-ergic neurons from the SCN inhibit the paraventricular nucleus
Paraventricular nucleus
The paraventricular nucleus is a neuronal nucleus in the hypothalamus. It contains multiple subpopulations of neurons that are activated by a variety of stressful and/or physiological changes. Many PVN neurons project directly to the posterior pituitary where they release oxytocin or vasopressin...
, which signals the superior cervical ganglion (SCG) through sympathetic
Sympathetic nervous system
The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's nervous system fight-or-flight response...
fibers. The output of the SCG, stimulates NE receptors (β
Adrenergic receptor
The adrenergic receptors are a class of metabotropic G protein-coupled receptors that are targets of the catecholamines, especially noradrenaline and adrenaline ....
) in the pineal gland
Pineal gland
The pineal gland is a small endocrine gland in the vertebrate brain. It produces the serotonin derivative melatonin, a hormone that affects the modulation of wake/sleep patterns and seasonal functions...
which produces N-acetyltransferase, causing production of melatonin from serotonin. Inhibitory melatonin receptors in the SCN then provide a positive feedback pathway
Neural pathway
A neural pathway, neural tract, or neural face, connects one part of the nervous system with another and usually consists of bundles of elongated, myelin-insulated neurons, known collectively as white matter...
. Therefore, light inhibits the production of melatonin which "entrains
Entrainment (chronobiology)
Entrainment, within the study of chronobiology, occurs when rhythmic physiological or behavioral events match their period and phase to that of an environmental oscillation. A common example is the entrainment of circadian rhythms to the daily light–dark cycle, which ultimately is determined by...
" the 24-hour cycle of SCN activity,. The SCN also receives signals from other parts of the brain, and its (approximately) 24 hour cycle does not only depend on light patterns. In fact, sectioned tissue from the SCN will exhibit daily cycle in vitro for many days. Additionally, (not shown in diagram), the basal nucleus provides GABA-ergic inhibitory input to the pre-optic anterior hypothalamus (PAH). When adenosine builds up from the metabolism of ATP throughout the day, it binds to adenosine receptors, inhibiting the basal nucleus. The PAH is then activated, generating slow-wave sleep activity. Caffeine
Caffeine
Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
is known to block adenosine receptors, thereby inhibiting sleep among other things.
Research
Research in neuropsychopharmacology comes from a wide range of activities in neuroscience and clinical research. This has motivated organizations such as the American College of Neuropsychopharmacology (ACNP), the European College of Neuropsychopharmacology (ECNP), and the Collegium Internationale Neuro-psychopharmacologicum (CINP) to be established as a measure of focus.The ECNP publishes European Neuropsychopharmacology, and as part of the Reed Elsevier Group, the ACNP publishes the journal Neuropsychopharmacology
Neuropsychopharmacology (journal)
Neuropsychopharmacology is a scientific journal published by the Nature Publishing Group. Since 1994, Neuropsychopharmacology has been the official publication of the ....
, and the CINP publishes the journal International Journal of Neuropsychopharmacology with Cambridge University Press
Cambridge University Press
Cambridge University Press is the publishing business of the University of Cambridge. Granted letters patent by Henry VIII in 1534, it is the world's oldest publishing house, and the second largest university press in the world...
.
In 2002 the most recent comprehensive collected work of the ACNP, "Neuropsychopharmacology: The Fifth Generation of Progress" was compiled. It is one measure of the current state of knowledge, and might be said to represent a landmark in the century-long goal to establish the basic neuro-biological principles which govern the actions of the brain.
Many other journals exist which contain relevant information such as Neuroscience
Neuroscience (journal)
Neuroscience is a peer-reviewed scientific journal published by Elsevier. The editor in chief is S.G. Lisberger Neuroscience is a peer-reviewed scientific journal published by Elsevier. The editor in chief is S.G. Lisberger Neuroscience is a peer-reviewed scientific journal published by Elsevier....
.
Some of them are listed at Brown University Library.
External links
- ACNP resources
- Organisations
- Collegium Internationale Neuro-psychopharmacologicum A global organisation dedicated to neuropsychopharmacology
- Journals
- Neuropsychopharmacology Journal - Official publication of the American College of Neuropsychopharmacology
- European Neuropsychopharmacology - An Elsevier journal
- The International Journal of Neuropsychopharmacology - A Cambridge University Press publication