BLOCKADE OF D-1 DOPAMINE-RECEPTORS IN THE MEDIAL PREFRONTAL CORTEX PRODUCES DELAYED-EFFECTS ON PRESYNAPTIC AND POSTSYNAPTIC INDEXES OF DOPAMINE FUNCTION IN THE NUCLEUS-ACCUMBENS

The present experiments assessed the acute and delayed effects of D-1 dopamine (DA) receptor blockade in the medial prefrontal cortex (mPFC) on pre- and postsynaptic indices of DA neurotransmission in the nucleus accumbens (N.Acc). Different groups of rats received intra-mPFC injections of saline (control animals) or the D-1 DA receptor antagonist SCH-23390 (0.25 mu g/side). Acutely, intra-mPFC injections of this antagonist did not affect spontaneous locomotion but significantly increased the locomotion induced by intra-N.Acc. amphetamine (1.5 mu g/side), in agreement with our earlier findings [Vezina et al. (1991) Eur. J. Neurosci., 3:1001-1007]. When tested two days post-injection, however, mPFC-SCH-23390 preexposed animals showed lower levels of locomotor activity than Control animals in response to intra-N.Acc. injections of amphetamine. This effect was not observed in other animals preexposed two days earlier to mPFC injections of amphetamine (2.5 mu g/side) or the D-2 DA receptor antagonist sulpiride (1.0 mu g/side). Animals preexposed two days earlier to mPFC SCH-23390 also showed higher levels of locomotor activity (+ 98%) when tested with intra-N.Acc. injections of the D-1 DA receptor agonist SKF-38393 (1.0 mu g/side) and a 36% increase in maximal DA-sensitive adenylate cyclase activity in comparison to Control animals. These effects were no longer observed in animals tested seven days following the mPFC SCH-23390 injections. These results demonstrate delayed actions resulting from cortical D-1 DA receptor blockade. They suggest, in a way consistent with previous findings [Herve et al. (1989) J. Neurosci., 9:3699-3708] that mPFC D-1 DA receptors are involved in the presynaptic regulation of DA neuron reactivity as well as the postsynaptic regulation of D-1 DA receptors in subcortical DA terminal and receptor fields such as the N.Acc.