The dopaminergic, glutamatergic, GABAergic bases for the action of amphetamine and cocaine.

The present experiments were designed to evaluate pharmacologically the role of three neuroanatomically related systems--dopamine, glutamate and GABA--in the motor-stimulant response to amphetamine and cocaine. The data indicate that stimulant-induced stereotypy is blocked by antagonists of all three systems and that agonists of all three systems administered into the striatum induce stereotypy. Furthermore, the interaction among them occurs in the striatum; and the reaction sequence, as determined by the effect of the relatively selective antagonists on agonist-induced stereotypy, appears to be a dopaminergic activation of a glutamatergic system which in turn activates a GABAergic system. Because the GABAergic system represents the major efferents from the striatum, the evidence suggests that the motor-stimulatory effects of amphetamine and cocaine result from a disinhibition of inhibitory systems in the thalamus, resulting in facilitation of excitation in the cortex.