Evidence for a differential medial prefrontal dopamine D1 and D2 receptor regulation of local and ventral tegmental glutamate and GABA release: a dual probe microdialysis study in the awake rat.

The effects of perfusion with two selective dopamine receptor agonists SKF38393 and pergolide into the medial prefrontal cortex (mPfc) on local and ventral tegmental area (VTA) glutamate and gamma-aminobutyric acid (GABA) release were investigated using dual probe microdialysis in the awake rat. Intracortical SKF38393 (10, 100, 500 microM, 60 min) decreased glutamate and increased GABA release in the mPfc but had no effect on either amino acid neurotransmitter in the VTA. Intracortical perfusion with the selective GABA(A) receptor antagonist bicuculline (0.1 microM, 140 min) reversed the SKF38393 (100 microM, 60 min)-induced decrease in local glutamate release, while the selective GABA(B) receptor antagonist CGP35348 (100 microM, 140 min) was without effect. Intracortical pergolide (1 microM, 60 min) was associated with a prolonged reversible decrease in local and VTA glutamate release that was also associated with a decrease in VTA GABA release, which was reversed in the presence of intracortical raclopride (10 microM, 140 min). Taken together, the present findings indicate a differential regulation of glutamate and GABA release in the mPfc and VTA by dopamine D(1) and D(2) receptors in the mPfc whereby (a) activation of the dopamine D(1) receptor in the mPfc decreases local glutamate release possibly via a feed-forward activation of the local GABA interneurons; (b) activation of the dopamine D(2) receptor in the mPfc inhibits both local glutamate release and the excitatory glutamate drive on the VTA.