INFLUENCE OF CHRONIC PRENATAL AND POSTNATAL ADMINISTRATION OF NALTREXONE IN LOCOMOTOR-ACTIVITY INDUCED BY MORPHINE IN MICE

The influence of chronic pre- and postnatal naltrexone exposure on the sensitivity of offspring to the locomotor effects of morphine was inv estigated in C-57 Black mice. Pregnant mice were injected subcutaneous ly (sc) with either saline (0.1 ml/10 g) or naltrexone (10 mg/kg) twic e daily during gestation and throughout lactation, 21 days postpartum. One, three and seven weeks after birth, male offspring were tested fo r locomotor activity. At 7 weeks of age, dose-response curves were obt ained with morphine (10, 31.6, and 100 mg/kg) and amphetamine(0.31, 10 and 31.6 mg/kg) in naltrexone-pretreated and in saline-treated animal s. Naltrexone exposure during gestation and lactation resulted in an a ugmented sensitivity of offspring to the locomotor activity-increasing effects of morphine. In these animals, the dose-response relationship for the effect of morphine on locomotor activity was displaced to the left about threefold. In contrast, naltrexone exposure did not alter the sensitivity of offspring to amphetamine. It was also found that of fspring of naltrexone-treated animals have significantly greater spont aneous locomotor activity than that of the offspring of saline-treated mothers. The increased locomotor activity persisted for at least 4 we eks after the last injection of naltrexone, These findings indicate th at chronic opioid receptor blockade during gestation and early postnat al development induces supersensitivity to the locomotor effects of mo rphine and is associated with long-lasting behavioral alterations.