Effect of perinatal buprenorphine exposure on development in the rat

The developmental effects of exposure to various doses of buprenorphine, methadone, or water during the perinatal period were studied in the rat. Rats were exposed to buprenorphine (0.3, 1.0, or 3.0 mg/kg/day), methadone (9 mg/kg/day), and/or water prenatally, postnatally, or both pre- and postnatally, via maternally implanted osmotic minipumps. Fetal and maternal mortality and morbidity were assessed, as well as the acquisition of several developmental milestones, pup weight gain, precipitated withdrawal, and the antinociceptive effect of morphine. Although perinatal exposure to buprenorphine failed to produce severe maternal and fetal or neonatal mortality, it was associated with a significant amount of perinatal mortality and perturbations of pup development. Pups developed physical dependence to both drugs, as evidenced by the ability of naloxone challenge to precipitate withdrawal. Both drugs induced tolerance to the antinociceptive effects of morphine in the tail-flick test. The effects of buprenorphine varied with the dose used, and the highest dose did not always produce the greatest effect. There were some similarities between the effects of perinatal buprenorphine and perinatal methadone; however, differences were also observed between the effects of the two drugs, which may be related to the different affinities and efficacies of the drugs at different opioid receptor subtypes.