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 a nd caudal halves of neostriatum and in the substantia nigra of adult r ats subjected to near total destruction of nigrostriatal dopamine neur ons by intraventricular 6-hydroxydopamine soon after birth. Three mont hs after this lesion, [H-3]SCH23390 binding (D1 receptors) was slightl y but significantly decreased in the rostral neostriatum (22%), but un changed in its caudal half and in the substantia nigra. In contrast, [ H-3]raclopride binding (D2 receptors) was considerably increased throu ghout the neostriatum (10-40%), while markedly decreased in the substa ntia nigra (80%). In the rostral neostriatum, there were no parallel c hanges in D2 receptor messenger RNA levels, as measured by in situ hyb ridization on adjacent sections. Caudally, however, slight but signifi cant increases in D2 messenger RNA could be observed (10-20%). As asse ssed by quantitative iontophoresis, there was a marked enhancement (63 %) of the inhibitory responsiveness of spontaneously firing units in t he rostral neostriatum to dopamine and the D, agonist, SKF38393, in ne onatally lesioned compared to control rats. On the other hand, respons iveness to PPHT, a potent D2 agonist, appeared to be unchanged. Such o pposite changes in the number of D1 and D2 binding sites, dissociated from the expression of D2 receptor messenger RNA and from the sensitiv ity to dopamine and D1 and D2 agonists, suggested independent adaptati ons of these various parameters following the neonatal dopamine denerv ation of neostriatum. They also provided further evidence for mechanis ms other than the dopamine innervation in the control of the expressio n of neostriatal D2 receptor messenger RNA during ontogenesis, and emp hasized that the effects of dopamine and its D1 and D2 agonists in neo striatum do not depend strictly on the number of D1 and D2 primary lig and recognition sites.