Focal bicuculline increases extracellular dopamine concentration in the nucleus accumbens of freely moving rats as measured by in vivo microdialysis.
This study was designed to assess the involvement of GABA(A) receptors in the regulation of in vivo dopamine release in the nucleus accumbens. Extracellular dopamine in the nucleus accumbens was measured using intracerebral microdialysis coupled with a high-performance liquid chromatography with electrochemical detection (HPLC-EC) system in freely moving Sprague-Dawley rats. Bicuculline, a GABA(A) receptor antagonist, and muscimol, a GABA(A) receptor agonist, were administered via a dialysis probe into the nucleus accumbens, respectively. The results showed that perfusion with bicuculline at concentrations of 25, 50, and 100 microM elicited a significant and concentration-dependent increase in extracellular dopamine in the nucleus accumbens. Dopamine levels returned to control values within 40-60 min after the termination of bicuculline perfusion. The increased dopamine produced by perfusion with 100 microM bicuculline was sensitive to sodium channel blockade with tetrodotoxin, and antagonized by co-perfusion with muscimol (25 and 50 microM) in a concentration-related fashion. Perfusion with 25 or 50 microM muscimol alone failed to alter basal levels of dopamine. The results suggest that local application of bicuculline increases dopamine release in the nucleus accumbens via a receptor-mediated process, and are consistent with the concept that basal dopamine release in the nucleus accumbens is under tonic inhibitory control by GABA(A) receptors within this structure.
Yan
Q
Q
Department of Biochemical and Therapeutic Sciences, University of Illinois College of Medicine at Peoria, 61656, USA. qsy@uic.edu
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists; D008297:Male; D017551:Microdialysis; D009068:Movement; D009118:Muscimol / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D009118:Muscimol; D013779:Tetrodotoxin; D004298:Dopamine; D001640:Bicuculline