The effects of adolescent morphine exposure on the sexual maturation of male rats, their reproductive capacity and the development of their progeny were examined. Groups of prepubescent male rates (25-27 days of age) were implanted with morphine- or placebo-pellets (one on Day 1, then two pellets on Days 4, 7 and 10); the pellets were not removed to assure the sustained release of morphine for 3 to 4 weeks and to avoid the confounding effects of a precipitated withdrawal syndrome. Groups of animals were sacrificed at weekly intervals through adulthood for an assessment of reproductive endocrine function. A large group, however, was also bred with drug-naive primiparous females at 85 days of age (8 weeks after morphine or placebo pellet implantation), when the acute and chronic effects of morphine on reproductive endocrine parameters had dissipated; their fertility and the development of the male and female progeny was characterized. Our results indicated that morphine exposure during adolescence led to a pronounced inhibition of a number of indices of sexual maturation (e.g., serum testosterone and luteinizing hormone levels and reduced weights of the testes and seminal vesicles). Breeding morphine- and placebo-implanted male rats with drug-naive females resulted in smaller liters derived from morphine-treated fathers when compared to controls, but in all other respects the development of the offspring in the two groups were equivalent. However, upon reaching adulthood, a number of selective endocrine differences were detected in morphine-derived offspring when compared to controls. Adult male offspring of morphine-treated males had significantly lower serum testosterone and luteinizing hormone levels. Hypothalamic β-endorphin levels were modestly elevated in male adult morphine-derived offspring, but these differences were not statistically significant. Adrenal weights were also significantly higher in morphine-derived male offspring, but serum corticosterone levels were within the normal range. A somewhat different pattern of endocrine deficits was observed in adult female morphine-derived offspring. Large increases in serum corticosterone levels were observed in female morphine-derived offspring and, in addition, β-endorphin levels in the hypothalamus were also significantly higher. In contrast to the male, no differences in reproductive endocrine status were observed in adult female morphine-derived offspring. Our data suggest that a period of exposure to opiates during adolescence cannot only influence markedly sexual maturation, but can also have long-term, selective and gender specific effects on endocrine function in their offspring.
|Number of pages||8|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - Jan 1 1991|