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. Efforts to induce sensitization or evoke expression with intrastriatal microinjections of amphetamine, NMDLA or THIP were not successful. The data indicate that these three neuroeffector systems interact at the level of the striatum to mediate the induction and expression of behavioral sensitization to amphetamine. The results are discussed in light of our previous reports and lead to the conclusion that two groups of drugs that affect sensitization can be defined: (1) antagonists of the dopaminergic, GABAergic and glutamatergic systems which block the acute effects of amphetamine as well as the induction and expression of sensitization and (2) another group of drugs which antagonize only sensitization-associated phenomena. The mouse data suggest that both the induction and the expression of sensitization involve not only multiple loci but also novel neuroeffector systems.