CHANGES OF D(1) AND D(2) RECEPTORS IN ADULT-RAT NEOSTRIATUM AFTER NEONATAL DOPAMINE DENERVATION - QUANTITATIVE DATA FROM LIGAND-BINDING, IN-SITU HYBRIDIZATION AND IONTOPHORESIS

The specific binding of [H-3]SCH23390 to D1 and of [H-3]raclopride to D2 dopamine receptors was measured by autoradiography in the rostral and caudal halves of neostriatum and in the substantia nigra of adult rats subjected to near total destruction of nigrostriatal dopamine neurons by intraventricular 6-hydroxydopamine soon after birth. Three months after this lesion, [H-3]SCH23390 binding (D1 receptors) was slightly but significantly decreased in the rostral neostriatum (22%), but unchanged in its caudal half and in the substantia nigra. In contrast, [H-3]raclopride binding (D2 receptors) was considerably increased throughout the neostriatum (10-40%), while markedly decreased in the substantia nigra (80%). In the rostral neostriatum, there were no parallel changes in D2 receptor messenger RNA levels, as measured by in situ hybridization on adjacent sections. Caudally, however, slight but significant increases in D2 messenger RNA could be observed (10-20%). As assessed by quantitative iontophoresis, there was a marked enhancement (63%) of the inhibitory responsiveness of spontaneously firing units in the rostral neostriatum to dopamine and the D, agonist, SKF38393, in neonatally lesioned compared to control rats. On the other hand, responsiveness to PPHT, a potent D2 agonist, appeared to be unchanged. Such opposite changes in the number of D1 and D2 binding sites, dissociated from the expression of D2 receptor messenger RNA and from the sensitivity to dopamine and D1 and D2 agonists, suggested independent adaptations of these various parameters following the neonatal dopamine denervation of neostriatum. They also provided further evidence for mechanisms other than the dopamine innervation in the control of the expression of neostriatal D2 receptor messenger RNA during ontogenesis, and emphasized that the effects of dopamine and its D1 and D2 agonists in neostriatum do not depend strictly on the number of D1 and D2 primary ligand recognition sites.