Behavioral evidence of depolarization block of mesencephalic dopamine neurons by acute haloperidol in partially 6-hydroxydopamine-lesioned rats.

The effects of acute haloperidol (HAL) and apomorphine (APO) administration were tested on the responsiveness of rats to medial forebrain bundle (MFB) brain stimulation reward (BSR) before and 28 days after partial dopamine (DA) depletion. Before 6-hydroxydopamine (6-OHDA) lesioning, HAL (50-100 micrograms/kg) and APO (25 micrograms/kg) both caused moderate decreases in the animals' responsiveness to BSR. In contrast, the same moderate doses of HAL completely abolished BSR after lesioning. However, postlesion responding for BSR after HAL could be reinstated by APO. The results of this study provide behavioral evidence that is consistent with recent electrophysiological data showing that acute HAL causes DA cells that survive 6-OHDA lesions to be driven into a state of depolarization block.