RELEASE OF ACETYLCHOLINESTERASE FROM GUINEA-PIG SUBSTANTIA-NIGRA - EFFECTS OF TRYPTAMINERGIC DRUGS AND DORSAL RAPHE NUCLEUS STIMULATION

The guinea-pig substantia nigra receives a 5-hydroxytryptaminergic (5-HT ergic) projection from the dorsal raphe 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 and the following receptor agonists were tested: 5-carboxamidotryptamine, sumatriptan, alpha-metyl-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 innefective at a similar concentration range. Electrical stimulation (50 Hz, 20-300 mu A) of the dorsal raphe nucleus evoked release of AChE from;he substantia nigra, and induced a rotational behavioural effect for the duration of stimulation. Pretreatment with 5,7-dihydroxytryptamine inhibited bath 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 raphe-stimulated AChE release. Drugs which inhibited raphe-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 raphe nucleus may be mediated in part via a 5-HT2 receptor type. The 5-HTID agonists 5-carboxamidotryptamine (10(-6) M) and sumatriptan (10(-5) M) also inhibited raphe-evoked AChE release, suggesting a possible presynaptic autoinhibitory role for 5-HTID receptors on raphe-nigral nerve terminals.