Non-DA prefronto-cortical efferents modulate D1 receptors in the nucleus accumbens.

Bilateral injections of 6-OHDA in the ventral mesencephalic tegmentum (VMT) destroy the DA afferents of the nucleus accumbens but do not induce any denervation supersensitivity of the D1 receptors in the nucleus accumbens. Because other non-DA afferent fibers might also regulate D1 receptors in that structure, bilateral ablations of the prefrontal cortex were performed. This lesion induced a 55% decrease of [3H]glutamic acid high-affinity uptake activity in the nucleus accumbens. When the prefronto-cortical ablation was performed simultaneously with the bilateral injection of 6-OHDA in the VMT, a marked hypersensitivity of DA-sensitive adenylate cyclase activity was observed in the nucleus accumbens (+52% increase of Vmax and a two-fold decrease of the Kapp for DA) while the ablation of the prefrontal cortex alone induced only a +14% (P less than 0.01) increase of D1 receptors in that structure. These results indicate that the regulation of D1 receptors in the nucleus accumbens is not solely dependent on the presynaptic DA innervation and that other non-DA fibers, such as those of the cortico-nucleus accumbens pathway, might contribute to it.