Alterations in dopamine release from striatal slices of rats after chronic treatment with haloperidol

The effects of chronic treatment with haloperidol on spontaneous and electrically evoked dopamine (DA) release from striatal slices of rats were investigated in vitro. DA was measured by high-performance liquid chromatography coupled to an electrochemical detector. The superfusion with haloperidol caused a dose-dependent (100 nM-100 microM) reduction in the electrically evoked DA release from striatal slices of rats, which was not antagonized by the superfusion with apomorphine. Chronic administration of haloperidol (1 mg/kg per day for 21 days) caused a significant reduction in electrically evoked DA release as well as in spontaneous DA release from striatal slices 24 h after the last injection. Moreover, pretreatment with haloperidol prevented the reduction of the DA release evoked in response to haloperidol superfusion (1 microM). These results indicated that chronic administration of haloperidol reduced DA release from striatal slices of rats, accompanied by tolerance for the inhibitory effect of drug superfusion on evoked DA release.