Morphine pretreatment increases opioid inhibitory effects on maternal behavior

Ongoing maternal behavior in rats is under the inhibitory influence of opia tes. Exposure to drugs of abuse may result in a progressive and enduring en hancement of their reinforcing effects. Little attention has been paid to t he possibility that puerperal treatment with morphine may lead to sensitiza tion to this drug, ultimately influencing the effects of opiates on materna l behavior. The aim of the present study was to investigate if the abrupt w ithdrawal of repeated treatment with morphine chlorhydrate (MC) during late pregnancy and early lactation may influence maternal behavior in lactating rats. The premise that a possible change in sensitivity to the inhibitory effect of MC on maternal behavior would last at least until day 17 of lacta tion without any reinforcement was tested. In addition, the hypothesis that the MC-induced inhibition would be reversed by the opioid antagonist nalox one was also tested. In all experiments female Wistar rats were treated wit h MG (5.0 mg/kg/day, subcutaneous [s.c.]) or saline for 7 days starting on the 17th day of pregnancy. After the abrupt discontinuation of long-term tr eatment, animals were acutely challenged with MC (5.0 mg/kg, s.c.) or salin e and tested for maternal behavior in three different experimental situatio ns: first, on days 5, 10, and 17 postpartum (Experiment 1); second, on day 17 postpartum (Experiment 2); third, on day 6 postpartum following naloxone pretreatment (1.0 mg/kg; Experiment 3). In Experiment 1, animals were trea ted for 7 days with morphine and acutely challenged with MC (group MM). Exp erimental MM animals showed significantly longer latencies for all maternal behavior parameters than all other groups during all observation days. The other groups (treated with MC for 7 days and acutely challenged with salin e, group MS; treated with saline for 7 days and acutely challenged with MC, group SM; and treated with saline for 7 days and acutely challenged with s aline, group SS) did not differ significantly from one another. In Experime nt 2, in which rats were submitted to a single test on day 17 of lactation, the MM group showed significantly longer latencies for all behavioral para meters as compared to group SM. Previous acute naloxone treatment (Experime nt 3) reversed the inhibitory effects of MC on maternal behavior in lactati ng rats. These data suggest that repeated administration of MC to female ra ts during late pregnancy sensitizes the animals to the inhibitory effects o f opioids on rat ongoing maternal behavior. (C) 2001 Elsevier Science Inc.