Persistent Spontaneous Oral Dyskinesias in Haloperidol-Withdrawn Rats Neonatally Lesioned with 6-Hydroxydopamine: Absence of an Association with the Bmax for [3H]Raclopride Binding to Neostriatal Homogenates

To investigate the influence of dopamine (DA) nerves on haloperidol (HAL)-induced oral dyskinesias, rats were first injected at 3 days after birth with 6-hydroxydopamine HBr (200 μg 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 every 10 min for 1 hr, increased from vs . intact rats drinking tap water). In HAL-treated 6-OHDA-lesioned rats, oral activity increased to >30 oral movements per session (P vs . HAL-treated intact rats). These levels of oral activity persisted in intact and 6-OHDA-lesioned rats as long as HAL was administered. After 11 months of HAL treatment, but 8 or 9 days after HAL withdrawal, DA was found to be reduced 97%, whereas serotonin was increased 29% in the striatum of 6-OHDA-lesioned rats. In HAL-treated intact and lesioned rats the B max for DA D 2 binding sites was elevated about 70%. With reverse 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 after 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 receptors. These findings demonstrate that in rats largely DA-denervated as 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.