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Dopamine

Dopamine

BIBLIOGRAPHY

Dopamine is a neurotransmitter that serves as a chemical messenger in the nervous system and permits individual nerve fibers (neurons) to communicate with each other. The dopamine neurotransmitter belongs to the class of compounds known as monoamines, and more specifically to a subclass of chemicals called catecholamines. Dopamine can act either as an inhibitory mechanism or an excitatory mechanism in the nervous system, depending on the location of dopamine neurons, and the receiving characteristics of the next neuron in the chain.

Dopamine activation has long been associated with increased motor output (i.e., increased physical activity) (Wise 2004). Hence, it is not surprising that dopamine depletion is associated with a variety of movement disorders, such as Parkinsons disease. Characterized by tremors, muscle rigidity, and lack of fine motor skills, Parkinsons is caused by a degeneration of dopamine projection fibers originating in a brain region called the substantia nigra. The fact that the administration of a substance (L-DOPA) that increases dopamine synthesis in this brain region is the primary approach to treating Parkinsonism underscores the importance of dopamine in the regulation of motor control and movement.

Changes in dopamine activity also are linked to the expression of certain psychological disorders, such as schizophrenia. Schizophrenia is characterized by shifting, illogical thought patterns, delusional thought processes, and hallucinations. The dopamine hypothesis of schizophrenia suggests that higher than normal levels of dopamine in the midbrain region of patients suffering from schizophrenia produce a biochemical imperative to engage in disordered behavior. Consistent with this position, the most commonly prescribed, and arguably the most effective, drug therapies for schizophrenia are dopamine receptor blockers. A compound labeled chlorpromazine (trade name Thorazine) is especially effective in reducing the symptoms of schizophrenia, and such dopamine antagonists when continued after treatment substantially lessen the chances for relapse compared to cases in which patients stop taking the drug.

There is evidence that blockade of dopamine transmission is associated with the devaluation of incentive systems, perhaps by affecting memory consolidation (Robbins and Everitt 2006). For instance, it is known that stamping-in of stimulus-response associations is blunted under conditions of reduced dopamine activity. Even once a behavior is learned, evidence shows that the ability to retrieve previously acquired information is reduced. Although the precise mechanisms responsible for these challenges to associative processes is not clear, it is clear that reward-seeking is diminished when dopamine systems are compromised.

There is a large literature that shows that a variety of rewarding events elevate the levels of dopamine in pleasure pathways of the brain. There are three major systems that are rich in dopamine fibers: the nigrostriatal system, the mesolimbic system, and the mesocortical system. Of the three, the pathway that has received the most attention from investigators of reward systems is the mesolimbic pathway. The dopamine projection neurons of the mesolimbic system originate in the ventral tegmental area of the midbrain and terminate in several forebrain regions, most importantly the nucleus accumbens. At one time it was believed that the nucleus accumbens constituted reward central and any events or substances that increased dopamine activity in this region served as rewards (Wise and Bozarth 1987). It is now known that other pathways and neurotransmitters are involved in defining reward properties, but the scientific community still maintains that elevated levels of dopamine in the nucleus accumbens contribute prominently to the rewarding effects associated with a variety of motivational processes, including the sex drive and hunger (Berridge and Robinson 1998).

Although dopamine plays a role in mediating a broad array of reinforcing (reward) activities, the topic that has been studied most is the modulatory role played by dopamine in determining the rewarding effects of psychoactive drugs. While dopamine is important for drugs such as heroin, marijuana, and alcohol, it does not appear to be crucial with respect to determining the reward value of these types of drugs. It is certain, however, that dopamine is the major neurotransmitter involved in defining the potency and addiction potential of psycho-stimulants such as cocaine and amphetamine. With respect to cocaine, the drug blocks the action of the dopamine transporter (DAT) in the nucleus accumbens. DAT is the reuptake chemical in the synaptic cleft (space between neurons where neurotransmitters are released) that moves dopamine back inside the releasing neuron and restores dopamine levels. When DAT is blocked by cocaine, dopamine remains in the cleft and continues to stimulate the postsynaptic neuron, thus producing euphoria. Amphetamine operates similarly to block dopamine reuptake, but also increases the frequency and amount of dopamine release.

SEE ALSO Happiness; Needs; Neuroscience; Psychology; Schizophrenia; Wants

BIBLIOGRAPHY

Berridge, K. C., and T. E. Robinson. 1998. What Is the Role of Dopamine in Reward: Hedonic Impact, Reward Learning, or Incentive Salience? Brain Research Review 28 (3): 309369.

Robbins, T. W., and B. J. Everitt. 2006. A Role for Mesencephalic Dopamine in Activation: Commentary on Berridge (2006). Psychopharmacology 191 (3): 433437.

Wise, Roy A. 2004. Dopamine, Learning, and Motivation. Nature Reviews in Neuroscience 5 (6): 483494.

Wise, Roy A., and Michael A. Bozarth. 1987. A Psychomotor Stimulant Theory of Addiction. Psychological Review 94 (4): 469492.

Jack Nation

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Dopamine

Dopamine


Dopamine belongs to a family of biological compounds called catecholamines (see Figure 1). Dopamine is synthesized from the compound L-dihydroxyphenylalanine (L-dopa) via the enzyme dopa decarboxylase. In noradrenergic neurons and in the adrenal glands, dopamine is the precursor for the neurotransmitter norepinephrine. In dopaminergic neurons, dopamine itself acts as a neurotransmitter. Although dopaminergic neurons are not as widely distributed in the brain as noradrenergic neurons, they act to coordinate movement, to control the secretion of some hormones, and to regulate mood and emotional stability.

Dopamine's role in the coordination of movement can be partially understood by examining Parkinson's disease. This illness is associated with low levels of dopamine in the brain and is characterized by spastic motion of the eyelids as well as rhythmic tremors of the hands and other parts of the body. One method of treating Parkinson's disease is to increase the concentration of dopamine in the brain. This is most effectively accomplished by administering the precursor of dopamine, L-dopa. In order to prevent concentrations of norepinephrine from increasing as well, L-dopa is given in conjunction with a drug that inhibits norepinephrine synthesis .

The role that dopamine plays in regulating mood and emotional stability can be at least partially grasped by examining dopamine's role in schizophrenia and drug addiction. Schizophrenia is a disorder characterized by delusions, hallucinations, withdrawal from external reality, and emotional unresponsiveness. The dopamine theory of schizophrenia, proposed in 1965, attributes the disorder to elevated brain concentrations of dopamine or to a hypersensitivity of dopaminergic receptors , especially the D2 and D4 receptor subtypes. Several drugs used to treat schizophrenic patients bind to D2 and D4 receptors and block the dopaminergic response.

Dopamine is also an important component of the brain's "reward system" and is believed to play a role in drug addiction. Increased levels of dopamine have been associated with cocaine, amphetamine , and marijuana use, as well as alcohol and nicotine addiction.

see also Neurotransmitters.

Jennifer L. Powers

Bibliography

Balter, Michael (1996). "New Clues to Brain Dopamine Control, Cocaine Addiction." Science 271:909.

Internet Resources

Indiana University School of Medicine, Terre Haute Center for Medical Education. The Medical Biochemistry Page. "Biochemistry of Nerve Transmission." Available from <http://web.indstate.edu/thcme/mwking/nerves.html>.

Northeastern University, Physical Therapy Department. Neuroanatomy Cyberlectures. "Pharmacology: The Chemistry of the Nervous System." Available from <http://www.ptd.neu.edu/neuroanatomy/cyberclass/Pharmacology>.

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dopamine

dopamine is a catecholamine, from which other important catecholamines (adrenaline and noradrenaline) are derived, but it is also an important neurotransmitter in its own right, especially in the brain. Of particular importance are central nervous pathways involved with the co-ordination of movement and with behaviour and emotion. As with the other catecholamines, dopamine is released from nerve endings where it acts upon receptors on other nerve cells to produce its effects. There are two sorts of receptors for dopamine, namely D1 and D2, of which the second are of greater importance. After release the dopamine is rapidly destroyed or taken up back into the nerve fibres for reuse. A number of medical conditions are associated with under-activity or over-activity of dopamine pathways in the brain. The rigidity and tremor, together with the hypokinesia (relative lack of voluntary movement), of Parkinson's disease are associated with lack of dopaminergic function in the nigrostriatal pathway in the brain. One form of treatment for this disease is to give large amounts of L-DOPA, the precurser of dopamine, so that some reaches the brain, is converted to dopamine, and restores some lost functions. Another approach is to transplant fetal dopamine-secreting cells into the relevant brain nuclei to take over the function of the diseased nerve cells. Over-activity of dopaminergic nerves, especially in the limbic system, is associated with schizophrenia. It has also been claimed that individuals with mutations affecting the dopamine D2 receptors show enhanced risk-taking behaviour. Some drugs, like the amphetamines, release dopamine from nerve endings in the brain, leading to hyperactivity and manic behaviour. Dopamine pathways are also associated with the vomiting centre in the brain, so drugs which block the dopamine receptors, such as the phenothiazines, have a calming effect on schizophrenics and are also useful anti-emetic drugs. There are a few dopamine pathways in other parts of the body, for example the kidney, where activation causes vasodilation. Dopamine increases the force of contraction of the heart and an infusion is sometimes used to treat shock resulting from blood loss.

Alan W. Cuthbert


See also basal ganglia; drug abuse.

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Dopamine

DOPAMINE

Dopamine (DA) is a catecholamine according to its chemical structure and a neurotransmitter of special importance for drug addiction. DA is a decarboxylated form of dopa (an amino acid) found especially in the basal ganglia. Chemically known as 3, 4 dihydroxyphenylethylamine, DA arises from dihydroxphenylacetic acid (dopa) by the action of the enzyme dopa decarboxylase. Dopamine-containing Neurons (nerve cells) are widespread in the brain and the body. Small interneurons are found in the autonomic ganglia, retina, hypothalamus, and medulla. Long axon neurons are found in two extensive circuits: (1) the nigrostriatal pathway links the substantia nigra neurons to the basal ganglia neurons and regulates locomotor events; (2) the mesocortical and mesolimbic circuits arise in the ventral tegmental area and project to the neocortex, limbic cortices, nucleus accumbens, and amygdala, where they regulate emotional events, including several forms of drug addiction, reinforcement, or reward. DA is also found in minute amounts in other catecholamine neurons as a precursor to norepinephrine. The DA transporter, which transports DA from outside the nerve terminal to inside the nerve terminal, functions to retrieve released DA and help terminate its action at receptors. The transporter is the target of psychostimulant drugs that produce their effects, at least in part, by blocking the transporter and preventing its removal from receptors. A consistent observation, for example, is the efflux of DA from nerve terminal regions in the nucleus accumbens in response to giving animals a psycho-stimulant such as cocaine or amphetamine. DA is also thought to be involved in schizophrenia and psychosis since DA-receptor-blocking drugs are clinically useful antipsychotic agents. Another disease, in which DA is lost due to the degeneration of DA-containing neurons, is Parkinson's disease, which can be treated by replacing DA with its precursor, dopa.

Floyd Bloom

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dopamine

dopamine (doh-pă-meen) n. a catecholamine derived from dopa that functions as a neurotransmitter, acting on specific dopamine receptors and also on adrenergic receptors throughout the body; it also stimulates the release of noradrenaline from nerve endings. Dopamine is used as a drug to increase the strength of contraction of the heart in heart failure, shock, severe trauma, and septicaemia. It is administered by injection in carefully controlled dosage.

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dopamine

dopamine Chemical normally found in the corpus striatum region of the human brain. Insufficient levels are associated with Parkinson's disease. Dopamine is a neurotransmitter and a precursor in the production of adrenaline and noradrenaline.

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dopamine

dopamine A catecholamine that is a precursor in the synthesis of noradrenaline and adrenaline. It also functions as a neurotransmitter, especially in the brain.

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dopamine

dopamine (dōp´əmēn), one of the intermediate substances in the biosynthesis of epinephrine and norepinephrine. See catecholamine.

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dopamine

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