Different regulations of dopaminergic (D1) receptors and neurotensinergic binding sites in the rat prefrontal cortex

The effects of the destruction of mixed dopamine/neurotensin (DA/NT) meso-cortical neurons were investigated by studying the development of denervation supersensitivity of DA (D1) and NT cortical post-synaptic binding sites using respectively 3H]SCH 23390 and 125I]NT as ligands. These neurons were destroyed bilaterally either by injection of 6-hydroxydopamine (6-OHDA) or by an electrolytic coagulation made in the ventral tegmental area (VTA). Five weeks later, both 3H]SCH 23390 and 125I]NT bindings were analysed by quantitative autoradiography on each lesioned animal and on corresponding controls. The chemical lesions of the VTA induced an increase in the density of the cortical NT binding sites but did not affect D1 binding sites. On the contrary, electrolytic lesions induced an increase in D1 binding sites and no change in NT binding sites. One possible explanation of these differences may be that, since chemical lesions of the VTA destroy noradrenergic (NA) ascending pathways while electrolytic lesions spare the cortical NA innervation, the observed modifications of D1 and NT cortical binding sites following their presynaptic denervation are dependent on the presence (increase in D1 receptors) or the absence (increase in NT binding sites) of the cortical NA innervation.