Regional differences in the induction of behavioral supersensitivity by prolonged treatment with atypical neuroleptics

Some atypical neuroleptics have been shown to exert selective effects on the nigrostriatal or mesolimbic dopamine systems as assessed by behavioral, biochemical and electrophysiological measures. This specificity appears to occur using chronic or acute schedules of drug administration. This study examined the effect of chronic administration of haloperidol, clozapine, sulpiride and metoclopramide on stereotypy and locomotor activity elicited by direct injection of dopamine in to the striatum or nucleus accumbens, respectively. Each rat was pre-treated with a neuroleptic drug or vehicle control for 21 days. Five days after the termination of drug treatment, each rat was injected with 10 μg dopamine bilaterally, and stereotypy or locomotor activity was measured. Rats pre-treated with metoclopramide exhibited an enhanced stereotypy response, and rats pre-treated with haloperidol, clozapine or sulpiride exhibited enhanced locomotor activity compared to controls. The extent to which these results demonstrate the selective action of these drugs in sensitizing dopamine systems is discussed.