Comparative development of D 1-dopamine and μ opiate receptors in normal and in 6-hydroxydopamine-lesioned neonatal rat striatum: dopaminergic fibers regulate μ but not D 1 receptor distribution

Abstract

The postnatal development of D 1 dopaminergic receptors (D 1 receptors) was investigated in the rat striatum in relation to distribution of μ opiate receptor patches and islandic tyrosine hydroxylase (TH)-immunoreactive fibers. The possible influence of dopaminergic (DA) fibers originating from the substantia nigra on the postnatal distribution of striatal D 1 and μ receptors was also examined by producing an early 6-hydroxydopamine (6-OHDA) lesion of DA fibers. D 1 and μ receptors were labelled with selective ligands: [ 3H]SCH 23390 and [ 3H]DAGO, respectively. During the first postnatal week, control rats showed patches of dense D 1 binding sites in the entire rostro-caudal extension of the striatum. The localization of D 1 receptor patches corresponded to striosomes identified by TH-immunoreactive islands. The striatal distribution of μ receptors was relatively homogeneous at postnatal day 0 (P0) but was clearly patchy at P3–P4. During the second postnatal week the striosomal pattern of D 1 binding sites disappeared along a dorso-ventral gradient whereas μ binding sites remained distributed in patches. Densitometric measurements showed that there was a parallel increase of D 1 binding sites in both striosomes and the surrounding matrix from P0 to P4. The disappearance of D 1 receptor patches observed in the dorsal striatum at P9 was due to a faster increase of D 1 binding sites in the matrix than in striosomes between P4 and P9 whereas a significant difference was still observed between these two compartments in the ventral striatum of P9 rats. During the third postnatal week, the density of D 1 binding sites still increased but became progressively uniform in the whole striatum. The intrastriatal injection of 6-OHDA in 2-day-old rats produced a local disappearance of TH-immunoreactive fibers in the striatum and a distal degeneration of TH-immunoreactive cell bodies in the substantia nigra. However an early lesion of striatal DA fibers did not modify the pattern of development or the density of D 1 binding sites during the postnatal period examined (1 and 3 weeks after the lesion). The distribution of μ receptors was unchanged 1 week after the lesion but showed a clear disorganization 3 weeks after the lesion. We discuss the differential influence of DA fibers on the distribution of D 1 and μ receptors in the rat striatum and the possible role of DA in the regulation of the expression of μ receptors.