Release of acetylcholinesterase from guinea-pig substantia nigra: effects of tryptaminergic drugs and dorsal raphé nucleus stimulation.

The guinea-pig substantia nigra receives a 5-hydroxytryptaminergic (5-HT ergic) projection from the dorsal raphé nucleus. In this study we have attempted to identify the 5-HT receptor subtype mediating release of acetylcholinesterase (AChE) from nigral neurones, measured by assay of perfusate obtained via chronically implanted push-pull cannulae. The effects of direct nigral application of 5-HT, 2-methyl-5-HT and 5-methoxytryptamine. Application of submicromolar concentrations of 5-HT, 2,5,-dimethoxy-4- iodoamphetamine and alpha-methyl-5-HT significantly enhanced release of AChE, whereas 5-carboxamidotryptamine, sumatriptan, 2-methyl-5-HT and 5-methoxytryptamine were ineffective at a similar concentration range. Electrical stimulation (50 Hz, 20-300 mu A) of the dorsal raphé nucleus evoked release of AChE from the substantia nigra, and induced a rotational behavioural effect for the duration of stimulation. Pretreatment with 5,7,-dihydroxytryptamine inhibited both DRN-evoked release of AChE and animal rotation. The 5-HT receptor antagonists ketanserin and ritanserin (10(-7)-10(-6)M, when applied to the substantia nigra, inhibited raphé-stimulated AChE release. Drugs which inhibited raphé-stimulated release of AChE had no effect on concomitant animal rotation, indicating that the behavioural events are mediated via distinct processes, unrelated to those mediating nigral AChE release. The data suggest that evoked release of AChE from the substantia nigra by stimulation of the dorsal raphé nucleus may be mediated in part via a 5-HT2 receptor type. The 5-HT1D agonists 5-carboxamidotryptamine (10(-6)M and sumatriptan (10(-5)M also inhibited raphé-evoked AChE release, suggesting a possible presynaptic autoinhibitory role for 5-HT1D receptors on raphé-nigral nerve terminals.