Dopamine modulates the inhibition induced by GABA in rat cerebral cortex: an iontophoretic study

Effects of iontophoresed gamma-aminobutyric acid (GABA) and two GABA agonists, 4,5,6,7-tetrahydroisooxazolo-[5,4-c]pyridine-3-ol (THIP) and baclofen were quantitatively compared in the anterior cingulate, frontal, and parietal cortex of urethane-anesthetized intact rats after catecholamine (CA) depletion with alpha-methyl-p-tyrosine (alpha-MPT) or selective dopamine (DA) denervation with 6-hydroxydopamine (6-OHDA). As assessed with to the IT50 index, the postsynaptic sensitivity to GABA was significantly higher in anterior cingulate than in frontal and parietal cortex. The responsiveness to GABA was also greater in frontal than in parietal cortex. Sensitivity to GABA was significantly reduced in both anterior cingulate and frontal cortex after CA depletion, and similarly, after DA denervation with 6-OHDA. The difference in the sensitivity to GABA between the three cortical regions in intact rats as well as after CA depletion did not seem to be correlated with either GABAA or GABAB receptors since the responsiveness to both GABA agonists in every region examined was comparable in intact rats, and remained unchanged after alpha-MPT treatment. This finding raises the possibility that some GABA receptors in the cerebral cortex may be pharmacologically distinct from the two main subtypes of GABA receptors, GABAA and GABAB. When GABA was administered by iontophoresis in the anterior cingulate cortex during continuous applications of subthreshold currents of DA, the inhibition induced by GABA was either increased or decreased. As DA innervation density is nearly two-fold greater in anterior cingulate than in frontal cortex, and 30-fold greater in anterior cingulate than in parietal cortex, these results suggest that responsiveness to GABA may be correlated with the regional density of DA innervation and that elevated levels of DA may enhance the sensitivity to GABA.