Chronic opioid receptor blockade during pregnancy: katernal and offspring effects

Chronic oplold receptor blockade in postnatal rats induced by the opioid antagonist naltrexone (NTX) has been shown to result in increases in body and organ weights, larger brain weights and areas, and precocious development of somatosensory and sensorimotor behaviors. To examine whether opioids are involved in prenatal development, time-mated nulliparous Sprague-Dawley rats were injected daily with 50 mg/kg NTX. At this dosage, NTX was found to block opioid receptors In the pregnant animals for 24 hr/day. No differences were observed in terns of gestation time, litter size, mortality, or incidence of congenital malformations between offspring of NTX and sterile water-injected controls (CO). However, birthwelghts of NTX-rats were significantly greater (25,9%) than CO pups. At birth, all rat pups were crossfostered to CO mothers. Mean body weights of the group given NTX prenatally were 18% to 41% larger than CO throughout the preweaning period. Crown-rump lengths and organ weights of NTX pups were greater relative to CO at 0, 10 and 21 days. These data suggest that (a) an endogenous opioid system related to somatic growth is present and functions in the prenatal rat, (b) opioids act as tonic negative regulators of growth, and (c) disruption of opioid-receptor interaction during fetal life has important implications in the postnatal period.