An investigation of the origin of extracellular GABA in rat nucleus accumbens measured in vivo by microdialysis.
GABA transmission in the nucleus accumbens is believed to play a central role in motivational processes and the expression of psychostimulant drug action. Here we report measurements of extracellular GABA in nucleus accumbens of the rat and investigate its origin. Extracellular GABA was detected using microdialysis in combination with a novel HPLC-based assay. In the awake rat, GABA in the microdialysates (1) increased 10-fold following perfusion with 0.5 mM nipecotic acid, a GABA releasing agent and uptake blocker, (2) increased 7-fold following local perfusion with 50 mM KCl, (3) decreased 50% following perfusion with tetrodotoxin, (4) decreased 50% following perfusion with a Ca(2+(-free medium and (5) decreased 40% following perfusion with high (12.5 mM) MgCl. Finally, in the anaesthetized rat, GABA in the microdialysates decreased 50% following i.p. injection of 100 mg/kg 3-mercaptoproprionic acid, a GABA synthesis inhibitor. We conclude that GABA in microdialysates from nucleus accumbens of the rat (awake) responds appropriately to selected pharmacological agents and derives at least in part (50%) from neurones.
Smith
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University Department of Clinical Pharmacology, Radcliffe Infirmary, Oxford, United Kingdom.
Sharp
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D015097:3-Mercaptopropionic Acid / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D004563:Electrochemistry; D005110:Extracellular Space / Q000378:metabolism*; D018756:GABA Antagonists / Q000494:pharmacology; D008274:Magnesium / Q000502:physiology; D008297:Male; D017551:Microdialysis; D009557:Nipecotic Acids / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018756:GABA Antagonists; D009557:Nipecotic Acids; C030278:nipecotic acid; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D011392:Proline; D015097:3-Mercaptopropionic Acid; C010983:homoproline; D008274:Magnesium; D011188:Potassium; D002118:Calcium