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 investigated in C-57 Black mice. Pregnant mice were injected subcutaneously (sc) with either saline (0.1 ml/10 g) or naltrexone (10 mg/kg) twice daily during gestation and throughout lactation, 21 days postpartum. One, three and seven weeks after birth, male offspring were tested for locomotor activity. At 7 weeks of age, dose-response curves were obtained 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 animals. Naltrexone exposure during gestation and lactation resulted in an augmented 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 offspring of naltrexone-treated animals have significantly greater spontaneous locomotor activity than that of the offspring of saline-treated mothers. The increased locomotor activity persisted for at least 4 weeks after the last injection of naltrexone. These findings indicate that chronic opioid receptor blockade during gestation and early postnatal development induces supersensitivity to the locomotor effects of morphine and is associated with long-lasting behavioral alterations.