Involvement of GABAA receptors in the regulation of the prefrontal cortex on dopamine release in the rat dorsolateral striatum

The characteristics of the prefrontal cortex regulation of dopamine release in the rat dorsolateral striatum were investigated in focusing on the corticostriatal pathway, using dual-probe microdialysis in combination with simple behavioral procedures. Intracortical perfusion of the GABA(A) receptor antagonist bicuculline (0.03 and 0.1 mM) increased the striatal dopamine release, whereas the GABA(A) receptor agonist muscimol (0.1 and 1 mM) reduced the release dose dependently. Co-perfusion of muscimol (0.01 mM), which did not by itself affect the dopamine release, completely prevented the glutamate (1 mM)-stimulated dopamine release and behavioral activities, including locomotion and rearing. Muscimol (0.01 mM) also prevented the N-methyl-D-aspartate (NMDA; 1 mM)-induced increases in glutamate, as well as dopamine levels. These findings suggest that the prefrontal cortex functionally regulates dopamine release in the dorsolateral striatum, which is mediated via GABA(A) receptors. This cortical GABAergic system underlying the prefrontal cortex regulatory mechanism appears to be associated with the corticostriatal pathway. (C) 2003 Elsevier B.V. All rights reserved.