THE ROLE OF DOPAMINE AND GABA IN THE FRONTAL-CORTEX OF MICE IN MODULATING A MOTOR-STIMULANT EFFECT OF AMPHETAMINE AND COCAINE

The results of previous studies have indicated that the activation of dopaminergic and GABAergic systems in the prefrontal cortex can decrea se dopaminergic and glutamatergic activity in the striatum, ostensibly by the inhibition of corticofugal glutamatergic pathways. The present studies were designed to investigate the cortical influence of dopami ne and GABA agonists and antagonists on the motor response to systemic ally administered amphetamine and cocaine in the mouse. The results sh ow that both dopamine and THIP, the GABA(A) agonist, injected intracor tically (IC) depress amphetamine-or cocaine-induced stereotypy. That t hese responses are functionally significant is illustrated by the IC e ffects of sulpiride and bicuculline; they enhance the motor activity o f the stimulants, suggesting that both dopaminergic and GABAergic syst ems in the cortex are activated by systemically administered amphetami ne or cocaine. Additional experiments demonstrated that bicuculline IC can antagonize the depressant effect of dopamine IC; therefore, the d opaminergic inhibition in the cortex appears to be mediated by the act ivation of a cortical GABA system. These results show that systemicall y administered amphetamine or cocaine causes dopaminergic effects not only in the striatum but also in the cortex, and that the dopaminergic effect in the cortex may activate a cortical GABAergic system, which in turn, may account for the noted cortical inhibition of the dopamine rgic motor-stimulatory action in the striatum. (C) 1998 Elsevier Scien ce Inc.