Multiple dopamine receptors and the behavioral effects of cocaine

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.