Interactions of Dopamine, Glutamate, and GABA Systems in Mediating Amphetamine- and Cocaine-Induced Stereotypy and Behavioral Sensitization

Abstract

The psychomotor stimulants are distinguished by their drug-abuse liability, their motor effects, and behavioral sensitization. How these effects relate to one another is not clear, but in the past, the studies of these stimulants have centered on dopamine and on the nucleus accumbens and the striatum, two areas of the brain that contain dopaminergic terminal fields, which historically have been implicated in the psychomotor effects of these drugs. The ever more detailed explication of neuroanatomy, specifi­cally of the basal ganglia, makes it obvious that, first, the characteristic actions of the psychomotor stimulants must involve transmitters other than dopamine and brain areas other than the accumbens and the striatum (1–6); second, the effects of the stimulants are mediated by the activation of circuits; third, the different pharmacological properties of the stimulants, such as a motor effect and sensitiza­tion, involve, in part, different circuits, even though they undoubtedly share some neuroeffector sys­tems. Starting with these working hypotheses, we initiated a study some 12 years ago that was designed to identify specific neuroeffectors and discrete brain areas that mediate a stimulant-induced motor effect and behavioral sensitization. The data presented below represent our observations on the general role of dopamine, glutamate, and GABA, as well as their specific functions in the straitum and in the frontal cortex, in enabling stimulant-induced stereotypy and behavioral sensitization.