Morphine pretreatment increases opioid inhibitory effects on maternal behavior

Ongoing maternal behavior in rats is under the inhibitory influence of opiates. Exposure to drugs of abuse may result in a progressive and enduring enhancement of their reinforcing effects. Little attention has been paid to the possibility that puerperal treatment with morphine may lead to sensitization to this drug, ultimately influencing the effects of opiates on maternal behavior. The aim of the present study was to investigate if the abrupt withdrawal 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 lactation without any reinforcement was tested. In addition, the hypothesis that the MC-induced inhibition would be reversed by the opioid antagonist naloxone was also tested. In all experiments female Wistar rats were treated with MC (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 treatment, animals were acutely challenged with MC (5.0 mg/kg, s.c.) or saline and tested for maternal behavior in three different experimental situations: 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 treated for 7 days with morphine and acutely challenged with MC (group MM). Experimental 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 saline, 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 saline, group SS) did not differ significantly from one another. In Experiment 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 parameters as compared to group SM. Previous acute naloxone treatment (Experiment 3) reversed the inhibitory effects of MC on maternal behavior in lactating rats. These data suggest that repeated administration of MC to female rats during late pregnancy sensitizes the animals to the inhibitory effects of opioids on rat ongoing maternal behavior.