PERSISTENT SPONTANEOUS ORAL DYSKINESIAS IN HALOPERIDOL-WITHDRAWN RATSNEONATALLY LESIONED WITH 6-HYDROXYDOPAMINE - ABSENCE OF AN ASSOCIATION WITH THE B-MAX FOR [H-3] RACLOPRIDE BINDING TO NEOSTRIATAL HOMOGENATES

To investigate the influence of dopamine (DA) nerves on haloperidol (H AL)-induced oral dyskinesias, rats were first injected at 3 days after birth with 6-hydroxydopamine HBr (200 mu g i.c.v., salt form; 6-OHDA) or vehicle, after desipramine HCl (20 mg/kg i.p., 1 hr) pretreatment. Two months later HAL (1.5 mg/kg/day, 2 days a week for 4 weeks, then daily for 10 months) was added to the drinking water of half the rats. Numbers of vacuous chewing movements, recorded in 1-min increments ev ery 10 min for 1 hr, increased from <5 to about 17 oral movements per session in intact rats, 14 weeks after instituting HAL (P < .01 vs. in tact rats drinking tap water). In HAL-treated 6-OHDA-lesioned rats, or al activity increased to >30 oral movements per session (P < .01 vs. H AL-treated intact rats). These levels of oral activity persisted in in tact and 6-OHDA-lesioned rats as long as HAL was administered. After 1 1 months of HAL treatment, but 8 or 9 days after HAL withdrawal, DA wa s found to be reduced 97%, whereas serotonin was increased 29% in the striatum of 6-OHDA-lesioned rats. In HAL-treated intact and lesioned r ats the B-max for DA D-2 binding sites was elevated about 70%. With re verse transcription polymerase chain reaction, the mRNA level for DA D -2L but not D-2S receptors was also found to be elevated about 70%. In a fraction of 6-OHDA-lesioned rats that were observed for 8 months af ter HAL withdrawal, oral activity persisted without decrement and was not accompanied by a change in the B-max or mRNA level for DA D-2 rece ptors. These findings demonstrate that in rats largely DA-denervated a s neonates, long-term HAL treatment produces an unusually high number of oral movements that persists for 8 months after HAL withdrawal and is not accompanied by an increase in DA D-2 receptor expression.