SYNERGISM BETWEEN D1 AND D2 DOPAMINE-RECEPTORS IN THE INHIBITION OF THE EVOKED RELEASE OF [H-3] GABA IN THE RAT PREFRONTAL CORTEX

In order to examine a possible interaction between D1 and D2 receptors in the dopaminergic control of the electrically-evoked release of [H-3]GABA in the rat prefrontal cortex, the effects of D1 and D2 dopamine agonists were studied in vitro on cortical slices. The D1 agonist SKF38393 (10(-5)M) inhibited the electrically-evoked release of [H-3]GABA. This effect was totally reversed by both the D1 antagonist SCH23390 (10(-7)M) and the D2 antagonist sulpiride (10(-5)M). We previously observed that maximal D2-mediated inhibition of the electrically-evoked release of [H-3]GABA was obtained with 10(-7)M RU24926 and 10(-8)M LY171555. Here we showed that the inhibition produced by these two D2 agonists is also abolished by 10(-7)M SCH23390. In dopamine-depleted slices from reserpine-treated animals, it was not possible to detect an effect of either RU24926 (10(-7)M) or SKF38393 (10(-5)M), suggesting a permissive role of endogenous dopamine in the effect of either D2 or D1 agonist. Finally, SKF38393 used at a subliminar concentration (10(-6)M) was able to potentiate the effect of a liminar concentration of RU24926 (1.5 x 10(-8)M). Taken together these results strongly suggest that in the rat prefrontal cortex a D1-D2 receptor synergism is involved in the dopaminergic control of the electrically-evoked release of [H-3]GABA.