The role of dopamine in the mouse frontal cortex: a new hypothesis of behavioral sensitization to amphetamine and cocaine.

In previous studies we demonstrated that dopamine, specifically a D2-receptor system, in the frontal cortex of the mouse functions to inhibit the motor response elicited by systemically administered amphetamine or cocaine; the inhibition appears to be the result of the dopaminergic activation of a GABAergic system. In the present study the inhibitory role of dopamine and GABA in the cortex was investigated in animals that were behaviorally sensitized to stimulant-induced stereotypy. For these studies various dopaminergic and GABAergic drugs were injected intracortically (i.

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 decrease 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 dopamine and GABA agonists and antagonists on the motor response to systemically administered amphetamine and cocaine in the mouse. The results show that both dopamine and THIP, the GABA(A) agonist, injected intracortically (i.

The role of the frontal cortex in the mouse in behavioral sensitization to amphetamine.

Pharmacological studies have shown that a variety of neuroeffectors are involved in behavioral sensitization to amphetamine-induced stereotypy. In the present work, the effect of some of these drugs on sensitization was studied after intracortical administration in order to determine the role of the cortex in mediating their systemic effects. The dopamine antagonists sulpiride and spiperone were both ineffective against the acute response to amphetamine; nevertheless, both blocked the induction of sensitization, suggesting that the mesocortical dopamine pathway is not involved in the acute response but is necessary for the induction of sensitization.

The role of the striatum in the mouse in behavioral sensitization to amphetamine.

Previous results of pharmacological studies of the mechanisms of amphetamine- and cocaine-induced stereotypy in the mouse suggest the involvement of dopaminergic, glutamatergic and GABAergic systems in the striatum. The present experiments were designed to evaluate pharmacologically the role of these neuroeffector systems in behavioral sensitization. Whether administered systemically or in the striatum, pretreatment with the neurotransmitter antagonists, sulpiride, bicuculline and CPP, blocked both the induction and the expression of behavioral sensitization.

A novel nicotinic-cholinergic role in behavioral sensitization to amphetamine-induced stereotypy in mice.

Cholinergic antagonists were used to investigate the role of the cholinergic system in amphetamine- and cocaine-induced behavioral sensitization to stereotypy in mice. Systemically, mecamylamine (1 mg/kg) and dihydro-beta-erythroidine (2 mg/kg) - nicotinic antagonists - and atropine (2 mg/kg) - a muscarinic antagonist - were ineffective against psychostimulant-induced stereotypy in naive animals. The nicotinic antagonists, however, blocked both the induction and expression of sensitization to amphetamine; in contrast, atropine was ineffective.