Cholinergic terminals in rat hippocampus possess 5-HT_1B receptors mediating inhibition of acetylcholine release

Abstract

The effects of 5-hydroxytryptamine (5-HT) on the release of [³H]acetylcholine ([³H]ACh) from rat hippocampal nerve endings were investigated using synaptosomes labelled with [³H]choline and depolarized in superfusion with 15 mM KCl. The release of [³H]ACh was concentration dependently inhibited by exogenous 5-HT. The concentration-response curve of 5-HT was shifted to the right in a parallel way by methiothepin. The 5-HT₂ antagonists ketanserin or methysergide did not antagonize the effect of 5-HT. The 5-HT₁ agonist 5-methoxy-3-[1,2,3,6-tetrahydropyridin-4-yl]-1H-indole (RU 24969) mimicked 5-HT, whereas the 5-HT_1A selective agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was ineffective. When used as a 5-HT_1A/5-HT_1B antagonist, (−)propranolol antagonized 5-HT whereas spiperone (a 5-HT_1A displacer) did not. The 5-HT_1C selective antagonist mesulergine was also ineffective towards 5-HT. It can be concluded that hippocampal cholinergic terminals are endowed with inhibitory 5-HT receptors which appear to belong to the 5-HT_1B subtype.