The role of endogenous opioid systems in preweaning cerebellar development was explored in rats utilizing naltrexone, a potent opioid antagonist. Sprague-Dawley rats were given daily subcutaneous injections of either 1 or 50 mg/kg naltrexone to invoke a temporary or complete blockade, respectively, of opioid receptors throughout the first 3 weeks of postnatal life; animals injected with sterile water served as controls. At weaning (day 21), macroscopic, morphometric, and histological determinations were conducted. In general, 50 mg/kg naltrexone had a stimulatory action on cerebellar development, whereas 1 mg/kg naltrexone had an inhibitory influence. Both sexes were affected comparably. Limits to naltrexone's ability to modulate cerebellar ontogeny were noted, with more latitude existing toward growth enhancement than impairment. The temporal course of ontogeny was generally unaltered in naltrexone-treated rats. Rather, only events that transpired over this period were dramatically affected. The most notable effects in 1 mg/kg naltrexone rats were marked decreases in cerebellar areal dimensions, the content of internal granule neurons, and cellular and tissue differentiation. Characteristics of the 50 mg/kg naltrexone group included increases in cerebellar areal dimensions, neural cell number, content, and size, and structural changes consistent with acceleration in growth and differentiation. Naltrexone influenced both neurons and glia, but only neural cells still being generated during the first 21 d after birth were altered in regard to quantity. Previous evidence has shown the presence of peak levels of endogenous opioids and opioid receptors in the cerebellum during the first weeks of life, as well as demonstrating the presence of enkephalin immunoreactivity on germinative cerebellar cells during postnatal neurogenesis but not in adult counterparts.(ABSTRACT TRUNCATED AT 250 WORDS)

The endogenous opioid peptide [Met5]-enkephalin is a tonically active opioid growth factor (OGF) with an inhibitory action on DNA synthesis in the developing rat retina. In this study, the ontogeny of the spatial and temporal expression of OGF and its binding activity was examined. OGF-like immunoreactivity was detected in the retina at gestation day (E) 20, but not at E18, and was localized to ganglion cell and neuroblast layers; immunochemical reaction was no longer seen in the retina by postnatal day 6. Native OGF was further identified and characterized by high-performance liquid chromatography (HPLC) studies and immunodot assays, which revealed that [Met5]-enkephalin was present in the neonatal, but not adult, rat retina. OGF binding activity was detected as early as E18 using [125I]-[Met5]-enkephalin and in vitro receptor autoradiography. Little OGF binding activity was noted for prenatal retinas, but appreciable activity was observed from birth to postnatal day 4; no OGF binding could be detected after postnatal day 5 or in the adult. These results reveal the transient appearance of the OGF, [Met5]-enkephalin, and its receptor binding activity in the developing mammalian retina, and show that their ontogeny coincides with the timetable of DNA synthesis of retinal neuroblasts.