Opioid antagonist (naltrexone) modulation of cerebellar development: histological and morphometric studies

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)