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

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 GABA_A agonist, muscimol, or the GABA_B 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.