5-HT2 RECEPTOR REGULATION OF ACETYLCHOLINE-RELEASE INDUCED BY DOPAMINERGIC STIMULATION IN RAT STRIATAL SLICES

The role of 5-hydroxytryptamine (5-HT) receptor subtypes in acetylchol ine (ACh) release induced by dopamine or neurokinin receptor stimulati on was studied in rat striatal slices. The dopamine D-1 receptor agoni st SKF 38393 potentiated in a tetrodotoxin-sensitive manner the K+-evo ked [H-3]ACh release while SCH 23390, a dopamine D-1 receptor antagoni st, had no effect. [H-3]ACh release was decreased by the dopamine D-2 receptor agonist LY 171555 (quinpirole) and slightly potentiated by th e dopamine D-2 receptor antagonist haloperidol. The selective neurokin in NK1 receptor agonist [Sar(9), met(O-2)(11)]SP also potentiated K+-e voked release of [H-3]ACh. GR 82334, a NK1 receptor antagonist, blocke d not only the effect of [Sar(9), met(O-2)(11)]SP but also the release of ACh induced by the D-1 receptor agonist SKF 38393. Among the 5-HT agents studied, only the 5-HT2C receptor antagonists ketanserin and ri tanserin were able to reduce the ACh release induced by dopamine D-1 r eceptor stimulation. Mesulergine, a more selective 5-HT2C antagonist, showed an intrinsic releasing effect but did not affect K+-evoked ACh release induced by SKF 38393. Methysergide and methiothepin, mixed 5-H T1/2 antagonists, as well as ondansetron, a 5-HT3 receptor antagonist, showed an intrinsic effect on ACh release, their effects being additi ve to that of SKF 38393. 5-HT2 receptor agonists were ineffective. How ever, the 5-HT2 agonist DOI was able to prevent the antagonism by keta nserin of the increased [H-3]ACh efflux elicited by SKF 38393, suggest ing a permissive role of 5-HT2A receptors. None of the above indicated 5-HT agents was able to reduce the ACh release induced by the selecti ve NK1 agonist. The results suggest that 5-HT2 receptors, probably of the 5-HT2A subtype, modulate the release of ACh observed in slices fro m the rat striatum after stimulation of dopamine D-1 receptors. It see ms that this serotonergic control is exerted on the interposed collate rals of substance P-containing neurons which promote ACh efflux throug h activation of NK1 receptors located on cholinergic interneurons.