INVIVO EVIDENCE FOR AN INHIBITORY GLUTAMATERGIC CONTROL OF SEROTONIN RELEASE IN THE CAT CAUDATE-NUCLEUS - INVOLVEMENT OF GABA NEURONS

The local effect of l-glutamic acid (5 × 10-5 M) on the release of [3H]serotonin continuously synthesized from [3H]tryptophan was examined in the caudate nucleus of 'encéphale isolé' unanaesthetized cats implanted with push-pull cannula. l-Glutamic acid (5 × 10-5 M) decreased [3H]serotonin release from nerve terminals of the dorsalis raphe-striatal serotonergic neurons. The effect was antagonized by 2-amino-6-triflurromethoxybenzothiazole (PK 26124) (10-6 M), an antagonist of glutamatergic transmission. This effect was mimicked by N-methoxy-d-aspartate acid NMDA (5 × 10-5 M) and prevented by dl-2-phosphono-valeric acid (APV) (5 × 10-5 M), indicating that l-glutamic acid decreased serotonin release via a N-methoxy-d-aspartate type receptor. The superfusion of serotonergic nerve terminals in the caudate nucleus with tetrodotoxin prevented the inhibitory l-glutamic acid-induced effect on serotonin release. Furthermore, l-glutamic acid-induced inhibition of [3H]serotonin release was antagonized by bicuculline (5 × 10-5 M). These data suggest that the glutamatergic receptors involved were not located directly on serotonin nerve terminals. The inhibitory control exerted by l-glutamic acid on serotonergic transmission could involve γ-aminobutyric acid interneurons. Since no reduction of spontaneous [3H]serotonin release was observed in the presence of bicuculline, GABAergic neurons appeared to exert a phasic influence on serotonin release. Indirect inhibitory presynaptic control on serotonin release mediated by corticostriatal glutamatergic fibers is discussed in light of previous findings. © 1990.