A comparative study of morphine treatment regimen prior to mating and during late pregnancy

Pre-mating treatment of female rats with morphine may have long-term effects. In this study, we analyzed the effects of two types of morphine sulfate pre-treatment: during pre-mating (5.0 mg/kg on alternate days for a total of seven doses) and during pregnancy (3.5 mg/(kgday) for 5 days starting on day 17 of pregnancy during early lactation. In order to evaluate possible morphine-induced behavioral changes, dams were tested for maternal behavior and locomotor activity during early lactation, and striatal and hypothalamic concentrations of dopamine and their metabolites and serum levels of corticosterone were measured. Maternal behavior was disrupted only in animals treated with morphine sulfate during pregnancy and challenged acutely (1.5 mg/kg) during lactation. Pre-mating treatment with morphine sulfate-induced changes in responses with increased locomotor activity, striatal dopamine turnover and serum corticosterone levels. None of these parameters were affected by morphine sulfate pre-treatment during late pregnancy. These data suggest that morphine has specific long-term and sometimes addictive-like effects on actively reproductive female animals that vary with the pre-treatment period, late pregnancy being particularly sensitive for effects on maternal behavior.