Characterization of extracellular GABA in the substantia nigra reticulata by means of brain microdialysis.
Brain microdialysis was used to characterize extracellular gamma-aminobutyric acid (GABA) in the substantia nigra reticulata (SNR) of freely moving rats. The extracellular GABA in the SNR was characterized using acutely implanted probes (4-8 h after surgery; day 1) and chronically implanted probes (24 h after surgery; day 2). 3-Mercaptopropionic acid, a glutamic acid decarboxylase inhibitor, was used to identify GABA. This drug induced an immediate decrease in the extracellular GABA levels to 40% of basal values, suggesting that the detected GABA is, at least in part, newly synthesized. The basal levels of extracellular GABA measured either on day 1 or day 2 were not affected by infusion of micromolar amounts of tetrodotoxin. Therefore, a direct coupling between GABA dialysate concentrations and nerve-impulse flow does not seem to exist. Infusion of the GABA uptake inhibitor nipecotic acid (0.5 mmol/l) resulted in a 4-fold increase in the dialysate levels of GABA lasting at least for 3 h on both days. K+ stimulation (60 mmol/l) increased extracellular GABA levels in the SNR to 450% of basal values. This effect again did not differ significantly on day 1 and day 2. The origin of the extracellular GABA in the SNR, as recorded by microdialysis under the two experimental conditions, is discussed.
Timmerman
W
W
Department of Medicinal Chemistry, University Centre for Pharmacy, Groningen, The Netherlands.
Zwaveling
J
J
Westerink
B H
BH
D015097:3-Mercaptopropionic Acid / Q000494:pharmacology; D000818:Animals; D003956:Dialysis; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D015097:3-Mercaptopropionic Acid; D011188:Potassium