In vivo characterization of extracellular GABA release in the caudate nucleus and prefrontal cortex of the rhesus monkey.
Extracellular gamma amino butyric acid (GABA) levels were measured in the caudate nucleus and the prefrontal cortex of the rhesus monkey brain using in vivo microdialysis under isofluorane gas anesthesia. Evoked GABA release was investigated for voltage sensitivity and calcium (Ca2+) dependency. There was a multifold increase in extracellular GABA levels following local perfusion with: (1) high potassium (50 mM, KCI), (2) veratridine (10 microM), and (3) the GABA releasing agent and uptake blocker, (-) nipecotic acid (1 mM). Release of GABA was significantly reduced when veratridine or (-) nipecotic acid were coinfused in Ca(2+)-free cerebrospinal fluid (CSF). Coinfusion of nipecotic acid with TTX (10 microM) also resulted in attenuation of evoked GABA release. These results suggest that GABA levels recovered using in vivo microdialysis, from the caudate nucleus and the prefrontal cortex in the rhesus monkey, derive in significant part from vesicular pools and the exocytotic process is both Ca(2+)-dependent and voltage-sensitive.
Kolachana
B S
BS
Clinical Brain Disorders Branch, NIMH/NIH, St. Elizabeths, Washington, D.C. 20032, USA.
Saunders
R C
RC
Weinberger
D R
DR
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism*; D002555:Cerebrospinal Fluid / Q000502:physiology*; D018682:GABA Agents / Q000494:pharmacology; D007263:Infusions, Parenteral; D008253:Macaca mulatta; D008564:Membrane Potentials / Q000187:drug effects; D017551:Microdialysis; D009557:Nipecotic Acids / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives*; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018682:GABA Agents; D009557:Nipecotic Acids; C030278:nipecotic acid; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D014701:Veratridine; D011392:Proline; C010983:homoproline; D011188:Potassium; D002118:Calcium