ENHANCED ORAL ACTIVITY RESPONSES TO INTRASTRIATAL SKF-38393 AND M-CPP ARE ATTENUATED BY INTRASTRIATAL MIANSERIN IN NEONATAL 6-OHDA-LESIONED RATS

Enhanced oral activity is induced in neonatal 6-hydroxydopamine- (6-OHDA-) lesioned rats by systemic administration of the dopamine (DA) D-1 receptor agonist SKF 38393 and serotonin (5-HT) 5HT(2A,2C) agonist m-chlorophenylpiperazine (rn-CPP). The DA D-1 receptor antagonist SCH 23390 effectively attenuates the effect of SKF 38393 but not m-CPP. The 5-HT(2)antagonist mianserin attenuates the effects of both m-CPP and SKF 38393, suggesting that DA agonist effects are mediated by 5-HT neurochemical systems. To test whether DA and 5-HT agonist effects and interactions might occur within the neostriatum, rats were implanted with permanent injection cannulae, with tips in the ventral striatum. One group of rats was lesioned at 3 days after birth with 6-OHDA HBr (100 mu g salt form, in each lateral ventricle; desipramine HCl pretreatment, 20 mg/kg IF, base form, 1 h), while controls received the vehicle in place of 6-OHDA. Cannulae were implanted when rats weighed 200-250 g. During a l-h observation session SKF 38393 (5 nmol per side) produced 74.3 +/- 19.2 oral movements in intact rats and 310.7 +/- 97.0 oral movements in 6-OHDA-lesioned rats. m-CPP (10 nmol per side) produced 72.6 +/- 15.1 and 274.5 +/- 65.0 oral movements in these respective groups. These responses were several-fold greater than the 25.3 +/- 7.3 and 41.8 +/- 9.5 oral movements in the same groups after saline (0.5 mu l per side) (P < 0.05). Mianserin (6 nmol per side) alone had no effect on oral activity but attenuated responses to both SKF 38393 and m-CPP in intact and 6-OHDA-lesioned rats. These findings demonstrate that enhanced oral activity responses are produced by intrastriatal SKF 38393 and m-CPP in neonatal 6-OHDA-lesioned rats. Also, when the 5-HT2 receptor antagonist mianserin was administered intrastriatally, induction of oral activity by the DB D-1 agonist SKF 38393 was attenuated. These findings indicate that ventral striatum represents at least one brain focus at which DA and 5-HT systems interact to modulate oral activity in rats.