Long-lasting effects of naltrexone, an opioid receptor antagonist, on cell proliferation in developing rat forebrain

Abstract Several studies have demonstrated in the past that endogenous opioid peptides and opioid receptors may be involved as mediators of brain tissue growth and function in the neonate. Applying histological and autoradiographic methods, we have examined the effect of the μ-receptor-specific antagonist, naltrexone, on the proliferation of the 4–12-week-old rat forebrain subependymal layer. We found that naltrexone, when given daily throughout the weaning period, evoked a long-lasting increase of the mitotic rate and the [ 3 H]thymidine labelling index. This effect was most significant about 8–10 weeks after ending the naltrexone treatment. Although a direct influence of naltrexone on long-term subependymal cell proliferation cannot be excluded, we are discussing evidence of an indirect effect via suppression of noradrenergic activity in the forebrain.