Modulation of GABA release by dopamine in the substantia nigra.
The role of specific dopamine receptor subtypes in the regulation of GABA release in the substantia nigra was investigated using microdialysis in the awake rat. Both basal and potassium-stimulated changes in the extracellular concentrations of GABA were examined in response to the local perfusion of tetrodotoxin (TTX), the D1 agonist SKF 38393, or the D2 agonist LY 171555 through the microdialysis probe in the substantia nigra. Although TTX (1 microM) did not alter the basal extracellular concentrations of GABA in the substantia nigra, it attenuated the potassium-stimulated (80 mM K+) release of GABA. SKF 38393 had no effect on basal extracellular concentrations of GABA, but did potentiate K+ -stimulated release of GABA in a concentration-dependent manner. The potentiated response at the highest concentration of SKF 38393 (100 microM) was blocked by the D1 antagonist SCH 23390. In contrast to the effect of the D1 agonist, the D2 agonist LY 171555 attenuated the stimulated release of GABA. These data indicate that although basal extracellular concentrations of GABA in the substantia nigra may not be derived from neuronal pools, K+ -stimulated release of GABA is impulse-mediated and is modulated by the D1 and the D2 receptors. Local interactions between dopamine and GABA in the substantia nigra may have important implications for the direct regulation of basal ganglia efferent activity and motor behavior.
Matuszewich
L
L
Department of Psychiatry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Yamamoto
B K
BK
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001481:Basal Metabolism; D001552:Benzazepines / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000502:physiology*; D013378:Substantia Nigra / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D011188:Potassium; D004298:Dopamine