Modulation of extracellular gamma-aminobutyric acid in the ventral pallidum using in vivo microdialysis

J Neurochem. 1992 Jun;58(6):2311-20. doi: 10.1111/j.1471-4159.1992.tb10979.x.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Baclofen / pharmacology
  • Calcium Channels / drug effects
  • Dialysis / methods
  • Dose-Response Relationship, Drug
  • Extracellular Space / chemistry
  • Extracellular Space / metabolism
  • Globus Pallidus / chemistry
  • Globus Pallidus / cytology
  • Globus Pallidus / metabolism*
  • 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
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Calcium Channels
  • Sodium Channels
  • Magnesium Chloride
  • Muscimol
  • Tetrodotoxin
  • gamma-Aminobutyric Acid
  • Veratridine
  • Verapamil
  • Baclofen
  • Potassium