Modulation of extracellular gamma-aminobutyric acid in the ventral pallidum using in vivo microdialysis.
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.
Bourdelais
A J
AJ
Department of VCAPP, Washington State University, Pullman 99164-6520.
Kalivas
P W
PW
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D003956:Dialysis / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism; D005917:Globus Pallidus / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D015636:Magnesium Chloride / Q000494:pharmacology; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D015222:Sodium Channels / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000032:analysis / Q000378:metabolism*
D015220:Calcium Channels; D015222:Sodium Channels; D015636:Magnesium Chloride; D009118:Muscimol; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D014701:Veratridine; D014700:Verapamil; D001418:Baclofen; D011188:Potassium