Influence of morphine exposure during adolescence on the sexual maturation of male rats and the development of their offspring

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.