Multiple dopamine receptors and the behavioral effects of cocaine. 1988

W L Woolverton, and M S Kleven
Department of Pharmacological and Physiological Sciences, University of Chicago, IL 60637.

Cocaine has a number of behavioral effects that are typical of psychomotor stimulants and likely involve DA mechanisms in the brain. These effects include, but are not limited to, reinforcing effects, discriminative stimulus effects, locomotor effects, effects on food intake, and effects on schedule-controlled behavior. The available data suggest that D-2 receptors are involved in the reinforcing effects of cocaine, although the jury is still out concerning the role of D-1 receptors. NE receptors apparently do not play a major role in this effect. The role of D-2 receptors in the discriminative stimulus effects is unclear because of partial substitution and partial blockade effects with D-2 agonists and antagonists, respectively. Data with D-1 agonists and antagonists suggest that D-1 receptors may play a necessary-but-not-sufficient role in the discriminative stimulus effects of cocaine. Moreover, results in several species suggest that NE may be important in this effect of cocaine. Very little data currently exist concerning the role of DA receptor subtypes in the other behavioral effects of cocaine. However, data with d-amphetamine suggest that D-1 as well as D-2 receptors should be investigated. In addition, there is evidence to suggest that NE is involved in some of cocaine's effects as well, an action that should be considered further. So, what mediates the behavioral effects of cocaine? Clearly, the answer is not a simple one, basically because the CNS pharmacology of cocaine is complex. In addition to the effects we have concentrated on, cocaine has effects on other neurotransmitters and local anesthetic effects that must be considered. It is impossible to say that any one pharmacological effect of cocaine mediates its behavioral effects, indeed even that it mediates any one behavioral effect. In fact, the word "mediates" is surely virtually meaningless in the context of the CNS. Perhaps the best that can be said about the role of DA receptors in the reinforcing effects of cocaine is they are likely a link in a chain of events that ultimately results in the sensations produced by cocaine. Surely numerous other, perhaps more critical, links remain to be discovered. It is an exciting time to be doing research with cocaine.

UI MeSH Term Description Entries
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D011954 Receptors, Dopamine Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells. Dopamine Receptors,Dopamine Receptor,Receptor, Dopamine
D012054 Reinforcement, Psychology The strengthening of a conditioned response. Negative Reinforcement,Positive Reinforcement,Psychological Reinforcement,Reinforcement (Psychology),Negative Reinforcements,Positive Reinforcements,Psychological Reinforcements,Psychology Reinforcement,Psychology Reinforcements,Reinforcement, Negative,Reinforcement, Positive,Reinforcement, Psychological,Reinforcements (Psychology),Reinforcements, Negative,Reinforcements, Positive,Reinforcements, Psychological,Reinforcements, Psychology
D001923 Brain Chemistry Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states. Chemistry, Brain,Brain Chemistries,Chemistries, Brain
D003042 Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Cocaine HCl,Cocaine Hydrochloride,HCl, Cocaine,Hydrochloride, Cocaine
D004193 Discrimination Learning Learning that is manifested in the ability to respond differentially to various stimuli. Discriminative Learning,Discrimination Learnings,Discriminative Learnings,Learning, Discrimination,Learning, Discriminative
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine

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