Serotonin autoreceptor in rat hippocampus: Pharmacological characterization as a subtype of the 5-HT1 receptor

Summary The 5-hydroxytryptamine (5-HT) autoreceptors mediating inhibition of [³H]5-HT release in rat hippocampus have been characterized pharmacologically in terms of 5-HT receptor subtype by using superfused synaptosomes depolarized with 15 mM KCl. Exogenous 5-HT inhibited in a concentration-dependent way (pEC₃₀=8.74) the K⁺-evoked release of [³H]5-HT. Methiothepin shifted the concentration-response curve of 5-HT to the right (pA₂=8.62). The 5-HT₂ receptor antagonists, ketanserin, methysergide or spiperone were ineffective against 5-HT. The 5-HT₁ receptor agonist, 5-methoxy-3-[1,2,3,6-tetra-hydropyridin-4-yl]-1H-indole (RU 24969) mimicked 5-HT and was equipotent as an inhibitor of the release of [³H]5-HT. In contrast, the putative 5-HT_1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was almost ineffective at 1 M. Finally, (–)propranolol, used as a non-selective 5-HT_1A/5-HT_1B receptor antagonist, shifted to the right (pA₂=7.91) the concentration-response curve of 5-HT whereas the 5-HT_1C receptor antagonist mesulergine was ineffective. In conclusion, 5-HT nerve terminals of rat hippocampus possess autoreceptors which appear to belong to the 5-HT_1B subtype.