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 dop amine depolarizes certain gamma-aminobutyric acid (GABA)-containing in terneurons in the cortex. We investigated the dopaminergic regulation of extracellular GABA levels in the prefrontal cortex using in vivo mi crodialysis. Systemic administration of the mixed D-1/D-2 dopamine rec eptor agonist apomorphine increased extracellular GABA levels in the p refrontal cortex, but did not increase levels of glycine; the apomorph ine-elicited increase in GABA levels was blocked by tetrodotoxin infus ion into the prefrontal cortex. Local administration of the D-2 agonis t quinpirole into the cortex via the dialysis probe resulted in a dose -dependent increase in extracellular GABA levels. In contrast, adminis tration of the D-1 agonist SKF 38393 did not alter GABA levels. The ab ility of systemic apomorphine to increase extracellular GABA levels in the prefrontal cortex was blocked by local administration of the D-2- like antagonist sulpiride to the cortex, but was not attenuated signif icantly by local perfusion of the D-1 antagonist SCH 23390. Similarly, the ability of local infusion of the D-1 agonist quinpirole to enhanc e extracellular GABA levels was blacked by sulpiride but not by SCH 23 390. These data suggest that dopamine agonists increase the release of GABA in the prefrontal cortex through a D-2-like receptor. In view of posited changes in prefrontal cortical dopamine and GABA systems in s chizophrenia, it is possible that changes in GABAergic function in the cortex in schizophrenia are secondary to changes in cortical dopamine function.