Both systemic and local administration of benzodiazepine agonists inhibit the in vivo release of 5-HT from ventral hippocampus.

The effects of benzodiazepine- and GABAA-receptor agonists and antagonists on the release and metabolism of 5-HT were measured in the ventral hippocampus of freely moving rats using microdialysis. Systemic injections of the benzodiazepine agonists, flurazepam and diazepam reduced the levels of 5-HT while the partial inverse agonist, FG 7142 (N-methyl-beta-carboline-3-carboxamide), had no effect. Local perfusion of flurazepam through the dialysis probe also decreased the release of 5-HT in the ventral hippocampus, an effect which was completely blocked by the benzodiazepine antagonist, Ro15-1788 (flumazenil). Local application of the GABAA agonist muscimol had no effect on the release of 5-HT, while the antagonist picrotoxin, administered locally, caused a 4-fold enhancement of release of 5-HT. Picrotoxin also resulted in a complete block of the inhibitory effect of flurazepam on release of 5-HT. None of these drugs caused significant changes in the levels of the metabolite of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) in the ventral hippocampus. These results suggest that the inhibitory effect of flurazepam on the release of 5-HT is mediated by benzodiazepine/GABAA receptors in the hippocampus and that GABA exerts a tonic inhibitory effect on the release of 5-HT in the region of the brain.