Serotonin-glutamate interaction in rat cerebellum: involvement of 5-HT1 and 5-HT2 receptors

Abstract The effects of serotonin (5-HT) on the release of endogenous glutamate (GLU) in rat cerebellum were investigated in slices depolarized with 35 mM K + . The Ca 2+ -dependent release of GLU was potently inhibited by 5-HT in a concentration-dependent way. Release was also inhibited by the 5-HT 1 receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and by the 5-HT 2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI). The inhibition by 10 nM 5-HT was partly (35–40%) counteracted by the 5-HT 2 receptor antagonist ketanserin but was fully blocked by the mixed 5-HT 1 /5-HT 2 receptor antagonist methiothepin. The effect of 8-OH-DPAT was not affected by ketanserin but was totally antagonized by methiothepin, while the effect of DOI was entirely suppressed by ketanserin. Ketanserin or methiothepin themselves increased (by 23 and 55%, respectively, at 10 nM) the K + -evoked release of GLU. In conclusion the release of endogenous GLU in rat cerebellum can be inhibited by 5-HT through receptors of the 5-HT 1 and 5-HT 2 type. The enhancement of GLU release by ketanserin or methiothepin could suggest a tonic inhibition. The possible localization of the 5-HT receptors involved in the interaction with the GLU systems is discussed.