CHLORDIAZEPOXIDE REDUCES INVIVO SEROTONIN RELEASE IN THE BASAL GANGLIA OF ENCEPHALE ISOLE BUT NOT ANESTHETIZED CATS - EVIDENCE FOR A DORSAL RAPHE SITE OF ACTION

  • 1 January 1983
    • journal article
    • research article
    • Vol. 226  (2) , 526-532
Abstract
By using a push-pull cannula technique and an isotopic method for the estimation of [3H]serotonin continuously synthetized from [3H]Trp, the effects of a benzodiazepine, chlordiazepoxide, were investigated on the in vivo release of [3H]serotonin in the cat basal ganglia. Chlordiazepoxide injection (10 mg/kg i.p.) decreased striatal and nigral [3H]serotonin release and enhanced the [3H] amine release in the dorsal raphe. These changes were blocked by the continuous superfusion of the dorsal raphe with Ro 15-1788 [ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo-[1,5-a] [1,4]-benzodiazepine-3-carboxylate] (10-5 M), a benzodiazepine receptor antagonist. Chlordiazepoxide (10-5 M) applied to the dorsal raphe reduced nigral [3H]serotonin release while decreasing [3H]serotonin release locally in the dorsal raphe. The superfusion of serotonergic nerve terminals of the substantia nigra or the caudate nucleus with chlordiazepoxide (10-5 M) never altered the local release of [3H]serotonin. The (inhibitory) influences exerted by chlordiazepoxide on serotonergic transmission apparently more likely involved cell bodies and/or dendrities rather than terminals of serotonergic neurons. Chlordiazepoxide-induced changes in [3H]serotonin release were only observed in encephale isole and not in halothane-anesthetized cats. GABAergic neurons of the dorsal raphe could participate to such a differential reactivity of serotonergic cells to chlordiazepoxide. [3H]-GABA release in the dorsal raphe was enhanced by halothane anesthesia. The influence exerted by benzodiazepines on serotonergic transmission, perhaps through a GABA-dependent process, can apparently significantly be involved in the pharmacological actions [antianxiety activity] of these drugs.