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

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Abstract
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.