ADVERSE-EFFECTS OF PATERNAL OPIATE EXPOSURE ON OFFSPRING DEVELOPMENT AND SENSITIVITY TO MORPHINE-INDUCED ANALGESIA

We have shown previously that chronic morphine administration to adole scent male rats produced a number of gender specific deficits in their offspring. The purpose of the present studies was to extend our earli er observations by examining the acute, direct effects of morphine exp osure to male rats on their fertility and the development of viable of fspring. Sexually mature male rats were injected with a single dose of morphine (25 mg/kg) and 24 hr later were bred with drug-naive females . Fertility rates (vaginal plugs and pregnancies) were monitored throu ghout the breeding period as was the development of the offspring. Our results showed that a large, acute dose of morphine given to drug-nai ve male rats 24 hr before the initiation of breeding had no effect on fertility rates, but produced several adverse effects on fetal outcome . Litter sizes in morphine-derived offspring were considerably smaller than in controls and mortality rates were more than 6 times higher. M oreover, morphine-derived male, but not female, offspring had a signif icantly enhanced sensitivity to the antinociceptive effects of morphin e. Collectively, these data suggest that acute paternal morphine expos ure just before breeding with drug-naive females had no effect on fert ility, but exerted negative effects on the viability and development o f their offspring. These results represent the most compelling evidenc e to date that paternal opiate exposure can adversely affect fetal out come and are particularly striking in that they were produced by a sin gle injection of morphine. We are aware of no animal studies, clinical cases or anecdotal reports in humans in which such a phenomenon has b een described.