Endogenous dopamine potentiates the effects of glutamate on extracellular GABA in the prefrontal cortex of the freely moving rat.
Using microdialysis, the effects of endogenous dopamine on basal extracellular concentrations of gamma-aminobutyric acid (GABA) and on the increases of GABA produced by glutamate were investigated in the medial prefrontal cortex of the awake rat. The dopamine uptake inhibitor nomifensine (1, 100 and 1000 microM), used to increase extracellular dopamine, produced a dose-related increase of dialysate dopamine (0.1-1 nM) but did not change dialysate concentrations of GABA or glutamate at any dose used. The glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxilic acid (PDC; 0.5 and 2 mM), used to increase extracellular glutamate, produced a dose-related increase of dialysate glutamate (1.5-5.5 microM) and increased dialysate GABA by 125%. When a simultaneous increase of endogenous dopamine and glutamate was produced, the increases of dialysate GABA were significantly higher (185% of baseline) than those produced by glutamate alone. These effects on dialysate GABA were attenuated by the D2 receptor antagonist (-) sulpiride, but not by the D1 receptor antagonist SCH-23390, all of which suggests that extracellular dopamine plays an important role in modulating endogenous glutamate-GABA interactions in the prefrontal cortex of the rat.
Del Arco
A
A
Department of Physiology, Faculty of Medicine, University Complutense, Madrid, Spain.
Mora
F
F
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D015314:Dialysis Solutions / Q000737:chemistry; D003998:Dicarboxylic Acids / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005110:Extracellular Space; D018698:Glutamic Acid / Q000494:pharmacology*; D008124:Locomotion; D008297:Male; D017551:Microdialysis; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D009627:Nomifensine / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000502:physiology; D013469:Sulpiride / Q000494:pharmacology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000187:drug effects* / Q000378:metabolism
D001552:Benzazepines; D015314:Dialysis Solutions; D003998:Dicarboxylic Acids; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D018765:Dopamine Uptake Inhibitors; D014179:Neurotransmitter Uptake Inhibitors; D011759:Pyrrolidines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D009627:Nomifensine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D013469:Sulpiride; C083486:pyrrolidine-2,4-dicarboxylic acid; D004298:Dopamine