SEROTONERGIC FACILITATION OF ACETYLCHOLINE-RELEASE IN-VIVO FROM RAT DORSAL HIPPOCAMPUS VIA SEROTONIN 5-HT3 RECEPTORS

The serotonin (5-HT) releaser d-fenfluramine and its active metabolite d-norfenfluramine, or the 5-HT-uptake inhibitor citalopram, by increa sing synaptic 5-HT availability, facilitated in vivo release of acetyl choline (ACh) from dorsal hippocampi of freely moving rats as determin ed by the microdialysis technique. The effects of d-norfenfluramine (7 .5 mg/kg i.p.) and citalopram (10 mu M, applied by reverse dialysis) w ere prevented by a 14-day chemical lesion of the raphe nuclei, suggest ing mediation by the 5-HT system in the cholinergic action of the drug s. The increase in extracellular ACh content induced by d-norfenfluram ine (5 mg/kg i.p.) was antagonized by the 5-HT3 receptor antagonists t ropisetron (0.5 mg/kg i.p.) and DAU 6215 (60 mu g/kg i.p.), but not by the mixed 5-HT1 and 5-HT2 receptor antagonist metergoline (2 mg/kg s. c.). In accordance with an involvement of the 5-HT3 receptor in the AC h facilitation induced by d-norfenfluramine is the finding that the se lective 5-HT3 receptor agonist 2-methylserotonin (250 mu g i.c.v., or 10 mu M applied by reverse dialysis) raised ACh release. The effect of the intracerebroventricular drug was prevented by the 5-HT3 antagonis ts DAU 6215 (60 mu g/kg i.p.) and ondansetron (60 mu g/kg s.c.). These antagonists by themselves did not modify the basal ACh release, indic ating that 5-HT does not tonically activate the 5-HT3 receptors involv ed. In conclusion, the overall regulatory control exerted by 5-HT in v ivo is to facilitate hippocampal ACh release. This is mediated by 5-HT 3 receptors probably located in the dorsal hippocampi.