Sunday, December 09, 2007

FYI: neurotransmitter and stuff: from Encyclopedia Britannica


also called chemical transmitter , or transmitter substance any of a group of chemical agents released by neurons (nerve cells) to stimulate neighbouring neurons, thus allowing impulses to be passed from one cell to the next throughout the nervous system.

The site where neurons meet is called the synapse and consists of the axon terminal (transmitting end) of one cell and the dendrite (receiving end) of the next. A microscopic gap called a synaptic cleft exists between the neurons. When a nerve impulse arrives at the axon terminal of one neuron, a chemical substance is released through the presynaptic membrane, traveling in milliseconds across the synaptic cleft to the postsynaptic membrane of the adjoining neuron. The chemical release is stimulated by the electrical activity of the neuron.

Although a large number of chemical substances are believed to act as
, only a few have been identified. Among those known are
acetylcholine, norepinephrine (noradrenalin), dopamine, and serotonin. Some chemical agents, such as acetylcholine, activate neurons, while others act as inhibiting substances.


also called neuronal junction the site of transmission of electric nerve impulses between two nerve cells (neurons) or between a neuron and a gland or muscle cell (effector). A synaptic connection between a neuron and a muscle cell is called a neuromuscular junction.

Art:Chemical transmission of a nerve impulse at the synapse

Chemical transmission of a nerve impulse at the synapse

At a chemical synapse each ending, or terminal, of a nerve fibre (presynaptic fibre) swells to form a knoblike structure that is separated from the fibre of an adjacent neuron, called a postsynaptic fibre, by a microscopic space called the
synaptic cleft. The typical synaptic cleft is about 0.02 micron wide. The arrival of a nerve impulse at the presynaptic terminals causes the movement toward the presynaptic membrane of membrane-bound sacs, or synaptic vesicles, which fuse with the membrane and release a chemical substance called a neurotransmitter.

This substance transmits the nerve impulse to the postsynaptic fibre by diffusing across the synaptic cleft and binding to receptor molecules on the postsynaptic membrane. The chemical binding action alters the shape of the receptors, initiating a series of reactions that open channel-shaped protein molecules. Electrically charged ions then flow through the channels into or out of the neuron. This sudden shift of electric charge across the postsynaptic membrane changes the electric polarization of the membrane, producing the
postsynaptic potential, or PSP. If the net flow of positively charged ions into the cell is large enough, then the PSP is excitatory; that is, it can lead to the generation of a new nerve impulse, called an action potential.

Once they have been released and have bound to postsynaptic receptors, neurotransmitter molecules are immediately deactivated by enzymes in the synaptic cleft; they are also taken up by receptors in the presynaptic membrane and recycled. This process causes a series of brief transmission events, each one taking place in only 0.5 to 4.0 milliseconds.

A single neurotransmitter may elicit different responses from different receptors. For example,
norepinephrine, a common neurotransmitter in the autonomic nervous system, binds to some receptors that excite nervous transmission and to others that inhibit it. The membrane of a postsynaptic fibre has many different kinds of receptors, and some presynaptic terminals release more than one type of neurotransmitter. Also, each postsynaptic fibre may form hundreds of competing synapses with many neurons.

These variables account for the complex responses of the nervous system to any given stimulus. The synapse, with its neurotransmitter, acts as a physiological valve, directing the conduction of nerve impulses in regular circuits and preventing random or chaotic stimulation of nerves.

Electric synapses allow direct communications between neurons whose membranes are fused by permitting ions to flow between the cells through channels called gap junctions. Found in
invertebrates and lower vertebrates, gap junctions allow faster synaptic transmission as well as the synchronization of entire groups of neurons. Gap junctions are also found in the human body, most often between cells in most organs and between glial cells of the nervous system. Chemical transmission seems to have evolved in large and complex vertebrate nervous systems, where transmission of multiple messages over longer distances is required.

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(ACh), an ester of choline and acetic acid that is the transmitter substance at many neural, or nerve, synapses and at the motor end plate of vertebrate muscles (see end-plate potential). When a nerve impulse arrives at the nerve ending, ACh, which is stored there in vesicles, is released and combines with a receptor molecule in the postsynaptic membrane or the end-plate membrane of a muscle fibre. This bonding changes the permeability of the membrane, and a change in the nature of a generator potential results. The effects of successive nerve impulses accumulate if they arrive at a sufficiently high frequency. The ACh is destroyed by an enzyme, acetylcholinesterase, and thus is effective only briefly. Inhibitors of the enzyme, however, prolong the lifetime of ACh itself.

ACh affects a number of body systems including the cardiovascular system by acting as a
vasodilator, by decreasing cardiac rate, and by decreasing cardiac contraction; the gastrointestinal system by such activities as increasing peristalsis in the stomach and by increasing the amplitude of digestive contractions; and the urinary tract by such actions as decreasing the capacity of the bladder and increasing the voluntary voiding pressure. It also affects the respiratory system and stimulates secretion by all glands that receive parasympathetic nerve impulses.

Art:Organization of the autonomic nervous system, showing the key role of acetylcholine in the …

Organization of the autonomic nervous system, showing the key role of acetylcholine in the …

ACh was first isolated around 1914; its functional significance was first established in about 1921 by
Otto Loewi, a German physiologist and later (1936) Nobel laureate. Loewi demonstrated that ACh is the substance liberated when the vagus nerve is stimulated, causing slowing of the heartbeat. Subsequently he and others showed that ACh is also liberated as a transmitter at the motor end plate of striated (voluntary) muscles of vertebrates, and it has since been identified as a transmitter at many neural synapses and in many invertebrate systems as well.

ACh is also known to play an important role in memory and learning and is in abnormally short supply in the brains of those with
Alzheimer's disease.

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also called Hydroxytyramine, a nitrogen-containing organic compound formed as an intermediate compound from dihydroxyphenylalanine (dopa) during the metabolism of the amino acid tyrosine. It is the precursor of the hormones epinephrine and norepinephrine. Dopamine also functions as a neurotransmitter—primarily by inhibiting the transmission of nerve impulses—in the substantia nigra, basal ganglia, and corpus striatum of the brain. A deficiency of dopamine results in Parkinson's disease (q.v.).

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also called 5-hydroxytryptamine, a chemical substance that is derived from the amino acid tryptophan. It occurs in the brain, intestinal tissue, blood platelets, and mast cells and is a constituent of many venoms, including wasp venom and toad venom. Serotonin is a potent vasoconstrictor and functions as a neurotransmitter. It is concentrated in certain areas of the brain, especially the midbrain and the hypothalamus, and changes in its concentration are associated with several mood disorders. Some cases of mental depression are apparently caused by reduced quantities or reduced activity of serotonin in the brain. Several antidepressant drugs achieve their effect by inhibiting the body's physiological inactivation of serotonin, resulting in the accumulation of that neurotransmitter in the brain (and a consequent elevation of mood). Conversely, excessive serotonin activity in the brain appears to cause such symptoms as migraines and nausea. The hallucinogenic compound LSD may act by inhibiting the action of serotonin.

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drug use
Popular misconceptions

Characteristics of drug use and abuse > The nature of drug addiction and dependence > Popular misconceptions

The bewilderment that the public manifests whenever a serious attempt is made to differentiate states of addiction or degrees of abuse probably stems from two all-too-common misconceptions concerning drug addiction. The first involves the stereotype that a drug user is a socially unacceptable criminal.

The carry-over of this conception from olden times is easy to understand but not very easy to accept today. Ironically, the so-called dope fiend, if indeed one does exist, is likely to be a person who is not using an opiate. The depressant action of opium and its derivatives is simply not consistent with the stereotype. The second misconception involves the naïve belief that there is something magically druglike about a drug, which makes a drug a drug.

Many substances are capable of acting on a biological system, and whether a particular substance comes to be considered a drug depends, in large measure, upon whether it is capable of eliciting a "druglike" effect that is valued by the user. There is nothing intrinsic to the substances themselves that sets one active substance apart from other active substances; its attribute as a drug is imparted to it by use.

Caffeine, nicotine, and alcohol are clearly drugs, and the habitual, excessive use of coffee, tobacco, or an alcoholic drink is clearly drug dependence if not addiction. The same could be extended to cover tea, chocolates, or powdered sugar, if society wished to use and consider them that way. The task of defining addiction, then, is the task of being able to distinguish between opium and powdered sugar while at the same time being able to embrace the fact that both can be subject to abuse.

This requires a frame of reference that recognizes that almost any substance can be considered a drug, that almost any drug is capable of abuse, that one kind of abuse may differ appreciably from another kind of abuse, and that the effect valued by the user will differ from one individual to the next for a particular drug, or from one drug to the next drug for a particular individual.
This kind of reference would still leave unanswered various questions of availability, public sanction, and other considerations that lead people to value and abuse one kind of effect rather than another at a particular moment in history, but it does at least acknowledge that drug addiction is not a unitary condition.

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The nature of drug addiction and dependence Popular misconceptions Physiological effects of addiction

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drug use
Physiological effects of addiction

Characteristics of drug use and abuse > The nature of drug addiction and dependence > Physiological effects of addiction

Certain physiological effects are so closely associated with the heavy use of opium and its derivatives that they have come to be considered characteristic of addictions in general. Some understanding of these physiological effects is necessary in order to appreciate the difficulties that are encountered in trying to include all drugs under a unitary definition that takes as its model opium.

is a physiological phenomenon that requires the individual to use more and more of the drug in repeated efforts to achieve the same effect. At a cellular level this is characterized by a diminishing response to a foreign substance (drug) as a result of adaptation. Although opiates are the prototype, a wide variety of drugs elicit the phenomenon of tolerance, and drugs vary greatly in their ability to develop tolerance.

Opium derivatives rapidly produce a high level of tolerance; alcohol and the barbiturates a very low level of tolerance. Tolerance is characteristic for morphine and heroin and, consequently, is considered a cardinal characteristic of narcotic addiction. In the first stage of tolerance, the duration of the effects shrinks, requiring the individual to take the drug either more often or in greater amounts to achieve the effect desired.

This stage is soon followed by a loss of effects, both desired and undesired.

Each new level quickly reduces effects until the individual arrives at a very high level of drug with a correspondingly high level of tolerance. Man can become almost completely tolerant to 5,000 milligrams of
morphine per day, even though a "normal," clinically effective dosage for the relief of pain would fall in the 5 to 20 milligram range. An addict can achieve a daily level that is nearly 200 times the dose that would be dangerous for a normal, pain-free adult.

Tolerance for a drug may be completely independent of the drug's ability to produce physical dependence. There is no wholly acceptable explanation for physical dependence.

It is thought to be associated with central-nervous-system depressants, although the distinction between depressants and stimulants is not as clear as it was once thought to be. Physical dependence manifests itself by the signs and symptoms of abstinence when the drug is withdrawn. All levels of the
central nervous system appear to be involved, but a classic feature of physical dependence is the "abstinence" or "withdrawal" syndrome.

If the addict is abruptly deprived of a drug upon which the body has physical dependence, there will ensue a set of reactions, the intensity of which will depend on the amount and length of time that the drug has been used. If the addiction is to morphine or heroin, the reaction will begin within a few hours of the last dose and will reach its peak in one to two days. Initially, there is yawning, tears, a running nose, and perspiration. The addict lapses into a restless, fitful sleep and, upon awakening, experiences a contraction of pupils, gooseflesh, hot and cold flashes, severe leg pains, generalized body aches and constant movement. The addict then experiences severe insomnia, nausea, vomiting, and diarrhea. At this time he has a fever, mild high blood pressure, loss of appetite, dehydration, and a considerable loss of body weight. These symptoms continue through the third day and then decline over the period of the next week. There are variations in the withdrawal reaction for other drugs; in the case of the barbiturates, minor tranquillizers, and alcohol, withdrawal may be more dangerous and severe. During withdrawal, drug tolerance is lost rapidly. The withdrawal syndrome may be terminated at any time by an appropriate dose of the addicting drug.

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Popular misconceptions Physiological effects of addiction Addiction, habituation, and dependence

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drug use
Addiction, habituation, and dependence

Characteristics of drug use and abuse > The nature of drug addiction and dependence > Addiction, habituation, and dependence

The traditional distinction between "addiction" and "habituation" centres on the ability of a drug to produce tolerance and physical dependence. The opiates clearly possess the potential to massively challenge the body's resources, and, if so challenged, the body will make the corresponding biochemical, physiological, and psychological readjustment to the stress.

At this point, the cellular response has so altered itself as to require the continued presence of the foreign substance (drug) to maintain normal function. When the substance is abruptly withdrawn or blocked, the cellular response becomes abnormal for a time until a new readjustment is made.

The key to this kind of conception is the massive challenge that requires radical adaptation. Some drugs challenge easily, but it is not so much whether a drug can challenge easily as it is whether the drug was actually taken in such a way as to present the challenge. Drugs such as caffeine, nicotine, bromide, the salicylates, cocaine, amphetamine and other stimulants, certain tranquillizers and sedatives are normally not taken in sufficient amounts to present the challenge.

They typically but not necessarily induce a strong need or craving emotionally or psychologically without producing the physical dependence that is associated with "hard" addiction. Consequently, their propensity for potential danger is judged to be less, so that continued use would lead one to expect habituation but not addiction. The key word here is expect. These drugs, in fact, are used excessively on occasion and, when so used, do produce tolerance and withdrawal signs.

Morphine, heroin, other synthetic opiates, and to a lesser extent codeine, alcohol, and the barbiturates, all carry a high propensity for potential danger in that all are easily capable of presenting a bodily challenge. Consequently, they are judged to be addicting under continued use. The ultimate effect of a particular drug, in any event, depends as much or more on the setting, the expectation of the user, his personality, and the social forces that play upon him, as it does on the pharmacological properties of the drug itself.

Enormous difficulties have been encountered in trying to apply these definitions of addiction and habituation because of the wide variations in the pattern of use. (The one common denominator in drug use is variability.)

As a result, in 1964 the World Health Organization recommended a new standard that replaces both the term drug addiction and the term drug habituation with the term drug dependence. Drug dependence is defined as a state arising from the repeated administration of a drug on a periodic or continual basis. Its characteristics will vary with the agent involved, and this must be made clear by designating drug dependence as being of a particular type—that is, drug dependence of morphine type, of cannabis type, of barbiturate type, and so forth.

As an example, drug dependence of a cannabis (marijuana) type is described as a state involving repeated administration, either periodic or continual. Its characteristics include
(1) a desire or need for repetition of the drug for its subjective effects and the feeling of enhancement of one's capabilities that it effects,
(2) little or no tendency to increase the dose since there is little or no tolerance development,
(3) a psychic dependence on the effects of the drug related to subjective and individual appreciation of those effects, and
(4) absence of physical dependence so that there is no definite and characteristic abstinence syndrome when the drug is discontinued.

Considerations of tolerance and physical dependence are not prominent in this new definition, although they are still conspicuously present. Instead, the emphasis tends to be shifted in the direction of the psychological or psychiatric makeup of the individual and the pattern of use of the individual and his subculture. Several considerations are involved here.

There is the concept of psychological reliance in terms of both a sense of well-being and a permanent or semipermanent pattern of behaviour.
There is also the concept of gratification by chemical means that has been substituted for other means of gratification.

In brief, the drug has been substituted for adaptive behaviour. Terms such as hunger, need, craving, emotional dependence, habituation or psychological dependence tend to connote a reliance on a drug as a substitute gratification in the place of adaptive behaviour.

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Physiological effects of addiction Addiction, habituation, and dependence Psychological dependence

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drug use
Psychological dependence

Characteristics of drug use and abuse > The nature of drug addiction and dependence > Psychological dependence

Several explanations have been advanced to account for the psychological dependence on drugs, but as there is no one entity called addiction, so there is no one picture of the drug user.

The great majority of addicts display "defects" in personality. Several legitimate motives of man can be fulfilled by the use of drugs. There is the relief of anxiety, the seeking of elation, the avoidance of depression, and the relief of pain. For these purposes, the several potent drugs are equivalent, but they do differ in the complications that ensue. Should the user develop physical dependence,
euphoric effects become difficult to attain, and the continued use of the drug is apt to be aimed primarily at preventing withdrawal symptoms.

It has been suggested that drug use can represent a primitive search for euphoria, an expression of prohibited infantile cravings, or the release of hostility and of contempt; the measure of self-destruction that follows can constitute punishment and the act of expiation. This type of psychodynamic explanation assumes that the individual is predisposed to this type of psychological adjustment prior to any actual experience with drugs. It has also been suggested that the type of drug used will be strongly influenced by the individual's characteristic way of relating to the world.

The detached type of person might be expected to choose the "hard" narcotics to facilitate indifference and withdrawal from the world. Passive and ambivalent types might be expected to select sedatives to assure a serene dependency. Passive types of persons who value independence might be expected to enlarge their world without social involvement through the use of hallucinogenic drugs, whereas the dependent type of person who is geared to activity might seek stimulants. Various types of persons might experiment with drugs simply in order to play along with the group that uses drugs; such group identification may be joined with youthful rebellion against society as a whole.

Obviously, the above descriptions are highly speculative because of the paucity of controlled clinical studies. The quest of the addict may be the quest to feel full, sexually satisfied, without aggressive strivings, and free of pain and anxiety. Utopia would be to feel normal, and this is about the best that the narcotic addict can achieve by way of drugs.

Although many societies associate addiction with criminality, most civilized countries regard addiction as a medical problem to be dealt with in appropriate therapeutic ways. Furthermore, narcotics fulfill several socially useful functions in those countries that do not prohibit or necessarily censure the possession of narcotics.

An old League of Nations report said: "The social and hygienic conditions under which a great part of the working classes in the Far East live are of so low a standard that these classes of people strive to find some form of diversion permitting them to forget at least for some moments the hardships of life." In addition to relieving mental or physical pain, opiates have been used medicinally in tropical countries where large segments of the population suffer from dysentery and fever.

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Addiction, habituation, and dependence Psychological dependence History of drug control

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Comment: The more we learn about life in general the most we will know about the root reasons and central causes of substance addiction. Nothing exists in-and-of itself. Reality is ultimately interconnected reality and nature seems to abhor a vacuum.

We should treat the suffering drug addict, but we need to also address the underlying problems and environmental social conditions that result in people seeking escapism and turning to drugs in order to cope with life or because of their failure to cope with life in their surrounding immediate environment. ~Peta-de-Aztlan

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