Effects of opioid agonist and antagonist in dams exposed to morphine during the perinatal period

The aim of the present work was to further analyse the features of opioid dependence following chronic morphine treatment during pregnancy and lactation. Dams from the day of mating were treated either with saline or with morphine (10 mg/kg) subcutaneously once daily. Physical and behavioural signs of morphine withdrawal were investigated both in the early postpartum period (maternal behaviour) and after weaning (physical signals, locomotion, anxiety-like behaviour). Maternal behaviour was evaluated after acute challenge with naloxone (3 mg/kg s.c.) or morphine (10 mg/kg s.c.) and morphine plus naloxone (10 mg/kg s.c. and 3 mg/kg s.c., respectively). After weaning sensitivity to the rewarding effect of morphine was measured by conditioned place preference and to the aversive effect of naloxone by conditioned place aversion tests. The intensity of physical and behavioural indices of dependence was also investigated by precipitation of withdrawal with naloxone (10 mg/kg s.c) after weaning. Naloxone impaired the maternal behaviour in morphine-treated dams but not in saline-ones. Acute challenge with morphine impaired maternal responsiveness both in saline and in morphine-treated dams, this effect of morphine, however could be completely antagonised by naloxone only in the saline-treated but not in the morphine-treated ones. Significantly increased sensitivity to the rewarding stimulus of morphine and more pronounced aversion to naloxone were observed in morphine-treated dams. Naloxone precipitated only moderate physical withdrawal signals in morphine-treated dams, while anxiety and locomotor activity after administration of naloxone (behavioural withdrawal) were not changed in them. In summary chronic, moderate dose morphine treatment during pregnancy and lactation resulted in only mild dependence, but it affected opioid-receptor sensitivity and presumably disrupted the functioning of endogenous opioid system.