Modulation of the Electrically Evoked Release of 5‐[3H]Hydroxytryptamine from Rat Cerebral Cortex: Effects of Alpidem, CL 218872, and Diazepam

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Abstract
The effect of ω (benzodiazepine)-receptor agonists, antagonists, and inverse agonists on the electrically evoked release of 5-[3H]hydroxytryptamine ([3H]5-HT) was studied in superfused slices of the rat frontal cerebral cortex. The electrically evoked release of [3H]5-HT was enhanced by nanomolar concentrations of diazepam and the selective oM1-receptor agonists alpidem and CL 218872. The ω/ω2- and ω1-receptor antagonists flumazenil and CGS 8216, respectively, did not modify the electrically evoked release of [3H]5-HT. The ω1-receptor agonist Ro 5–4864 and the ω1-receptor inverse agonist ethyl-β-carboline-3-carboxylate on their own did not affect the electrically evoked release of [3H]5-HT. On the other hand, the inverse agonist 6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylic acid methyl ester (DMCM), at micromolar concentrations, inhibited both the spontaneous and the evoked release of [3H]5-HT. The facilitation of the electrically evoked release of [3H]5-HT by diazepam, alpidem, or CL 218872 was potentiated by γ-aminobutyric acid (GABA). Exposure to flumazenil and CGS 8216 antagonized the facilitation by diazepam, alpidem, or CL 218872 of [3H]5-HT release. The inhibition of the release of [3H]5-HT by DMCM was not modified by exposure to either flumazenil, CGS 8216, or GABA. The inhibitory effect of DMCM was not observed when monoamine oxidase activity was inhibited by pargyline. Our results indicate that activation of ω1-re-ceptors by agonists facilitates the electrically evoked release of [3H]5-HT from slices of the rat frontal cerebral cortex, and that these ω1-receptors appear to be associated in a macromolecular complex with the GABA receptor. Inverse agonists acting on the ω1-GABA receptor complex are not involved in the modulation of the release of [3H]5-HT.