Perinatal exposure to morphine disrupts brain norepinephrine, ovarian cyclicity, and sexual receptivity in rats

The effect of perinatal exposure to morphine on the development of catecholaminergic and reproductive function in female rats was investigated. Adult rats received morphine intraperitoneally daily for 40 days. The dose of morphine was progressively increased at 10-day intervals from 5, 7.5, 10 to 15 mg/kg body weight until day 40. The rats were mated between days 38 and 45. Administration of morphine at dose rates of 20 and 30 mg/kg continued during pregnancy. The dose was increased to 40 mg/kg for 10 days postpartum. Results showed that morphine disrupted ovarian cyclicity in 52% of the females. Amongst the remaining females, 43% became pregnant when mated. In the female offspring born to such dams, sexual maturation was delayed and body weight was reduced until weaning. At adulthood, lordosis behavior was inhibited when the female offspring were tested against stimulus males. Plasma estradiol and ovarian estradiol and progesterone levels were reduced. Norepinephrine concentration in the hypothalamus was reduced, whereas it remained unchanged in the amygdala. Dopamine concentrations in both hypothalamus and amygdala were not influenced by perinatal morphine exposure. These results suggest that chronic morphine treatment during perinatal life selectively influences the development of noradrenergic mechanisms in the rat brain and this may in turn be responsible for reduced reproductive activity.