Modulation of Extracellular γ‐Aminobutyric Acid in the Ventral Pallidum Using In Vivo Microdialysis

: Intracranial microdialysis was used to investigate the origin of extracellular γ‐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 Ca2+‐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 predominately Ca2+‐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 Ca2+‐ or Na+‐dependent mechanisms. They also suggest that Na+‐dependent release of GABA via reversal of the uptake carrier can be shown in vivo.