Chronic treatment with haloperidol modifies the sensitivity of autoreceptors that modulate dopamine release in rat striatum.

The effects of apomorphine or sulpiride on electrically evoked dopamine release from striatal slices of rats pretreated with haloperidol were investigated. Chronic haloperidol treatment (1 mg/kg per day for 21 days) significantly reduced electrically evoked dopamine release from striatal slices until 72 h after the last injection. The apomorphine-induced reduction and the sulpiride-induced increase in evoked dopamine release were significantly enhanced by the chronic treatment with haloperidol at 72 h after the last injection. The enhancement of the sulpiride-induced increase in evoked dopamine release was inversely correlated with the dopamine release evoked by the first stimulation in striatal slices from haloperidol-treated (r = -0.85, n = 12, P < 0.01) but not from saline-treated rats. These results suggest that an increase in the sensitivity of dopamine autoreceptors due to chronic treatment with haloperidol could partially account for the reduction in dopamine release from striatal slices of rats.