Article date: 1992/6/1
PubMed ID: 1315380
Journal name: Journal of neurochemistry (ISSN: 0022-3042)
Intracranial microdialysis was used to investigate the origin of extracellular gamma-aminobutyric acid (GABA) in the ventral pallidum. Changes in basal GABA levels in response to membrane depolarizers, ion-channel blockers, and receptor agonists were determined. Antagonism of Ca2+ fluxes with high Mg2+ in a Ca(2+)-free perfusion buffer decreased GABA levels by up to 30%. Inhibition of voltage-dependent Na+ channels by the addition of tetrodotoxin also significantly decreased basal extracellular GABA concentrations by up to 45%, and blockade of Ca2+ and Na+ channels with verapamil reduced extracellular GABA by as much as 30%. The addition of either the GABAA agonist, muscimol, or the GABAB agonist, baclofen, produced a 40% reduction in extracellular GABA. GABA release was stimulated by high K+ and the addition of veratridine to increase Na+ influx. High K(+)-induced release was predominantly Ca(2+)-dependent, whereas the effect of veratridine was potentiated in the absence of extracellular Ca2+. Both high K(+)- and veratridine-induced elevations in extracellular GABA were inhibited by baclofen, whereas only veratridine-induced release was antagonized by muscimol. These results demonstrate that at least 50% of basal extracellular GABA in the ventral pallidum is derived from Ca(2+)- or Na(+)-dependent mechanisms. They also suggest that Na(+)-dependent release of GABA via reversal of the uptake carrier can be shown in vivo.
Author List: Bourdelais A J, Kalivas P W
Publication Types: Journal Article; Research Support, U.S. Gov't, P.H.S.
Substances mentioned in the article: Calcium Channels; Sodium Channels; Magnesium Chloride; Muscimol; Tetrodotoxin; gamma-Aminobutyric Acid; Veratridine; Verapamil; Baclofen; Potassium;
Mesh terms: Animals; Baclofen/pharmacology; Calcium Channels/drug effects; Dialysis/methods; Dose-Response Relationship, Drug; Extracellular Space/chemistry; Globus Pallidus/chemistry; Magnesium Chloride/pharmacology; Male; Muscimol/pharmacology; Neurons/physiology; Potassium/pharmacology; Rats; Rats, Inbred Strains; Sodium Channels/drug effects; Tetrodotoxin/pharmacology; Verapamil/pharmacology; Veratridine/pharmacology; gamma-Aminobutyric Acid/analysis;