Dopaminergic regulation of extracellular gamma-aminobutyric acid levels in the prefrontal cortex of the rat.
Dopaminergic axons in the prefrontal cortex synapse with interneurons as well as pyramidal cells. Electrophysiological data suggest that dopamine depolarizes certain gamma-aminobutyric acid (GABA)-containing interneurons in the cortex. We investigated the dopaminergic regulation of extracellular GABA levels in the prefrontal cortex using in vivo microdialysis. Systemic administration of the mixed D1/D2 dopamine receptor agonist apomorphine increased extracellular GABA levels in the prefrontal cortex, but did not increase levels of glycine; the apomorphine-elicited increase in GABA levels was blocked by tetrodotoxin infusion into the prefrontal cortex. Local administration of the D2 agonist quinpirole into the cortex via the dialysis probe resulted in a dose-dependent increase in extracellular GABA levels. In contrast, administration of the D1 agonist SKF 38393 did not alter GABA levels. The ability of systemic apomorphine to increase extracellular GABA levels in the prefrontal cortex was blocked by local administration of the D2-like antagonist sulpiride to the cortex, but was not attenuated significantly by local perfusion of the D1 antagonist SCH 23390. Similarly, the ability of local infusion of the D2 agonist quinpirole to enhance extracellular GABA levels was blocked by sulpiride but not by SCH 23390. These data suggest that dopamine agonists increase the release of GABA in the prefrontal cortex through a D2-like receptor. In view of posited changes in prefrontal cortical dopamine and GABA systems in schizophrenia, it is possible that changes in GABAergic function in the cortex in schizophrenia are secondary to changes in cortical dopamine function.
Grobin
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AC
Department of Pharmacology and Psychiatry, Yale University School of Medicine, New Haven, Connecticut 37212, USA.
Deutch
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AY
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000187:drug effects* / Q000378:metabolism
D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D005680:gamma-Aminobutyric Acid; D001058:Apomorphine