Article date: 1989/10/1
PubMed ID: 2478921
Journal name: Neuropharmacology (ISSN: 0028-3908)
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.
Author List: Pei Q, Zetterström T, Fillenz M
Publication Types: Journal Article; Research Support, Non-U.S. Gov't
Substances mentioned in the article: Carbolines; Ion Channels; Receptors, GABA-A; Picrotoxin; Benzodiazepines; Muscimol; Serotonin; Flumazenil; Hydroxyindoleacetic Acid; FG 7142; Flurazepam; Diazepam;
Mesh terms: Animals; Benzodiazepines/pharmacology; Carbolines/pharmacology; Chromatography, High Pressure Liquid; Dialysis; Diazepam/pharmacology; Flumazenil/pharmacology; Flurazepam/pharmacology; Hippocampus/drug effects; Hydroxyindoleacetic Acid/metabolism; Ion Channels/drug effects; Male; Muscimol/pharmacology; Picrotoxin/pharmacology; Rats; Rats, Inbred Strains; Receptors, GABA-A/drug effects; Serotonin/metabolism;