Regionally specific effects of haloperidol and clozapine on dopamine reuptake in the striatum

This study examined the extent to which local application of the typical neuroleptic haloperidol (HAL) or the atypical neuroleptic clozapine (CLOZ) influences dopamine (DA) transporter function in the dorsal and ventral striatum. Using urethane-anesthetized rats, DA was pressure ejected and monitored with in vivo electrochemistry, into the dorsal and ventral striatum to establish regional baseline DA reuptake rates. Haloperidol or CLOZ (10 microM) was then applied, followed 5 min later by DA, in order to assess drug effects on DA reuptake rates. Haloperidol caused a 62% decrease in dorsal striatal DA reuptake rates while CLOZ had no effect on reuptake rates. Neither neuroleptic significantly altered DA reuptake rates in the ventral striatum. It is possible that HAL-induced decrease in DA reuptake in the sensorimotor striatum could be related to the motor side effect profile of this neuroleptic. Additional studies with other typical and atypical neuroleptics are needed to further evaluate the relationship between slowing of DA reuptake and the side effect potential of neuroleptic agents.