PERINATAL METHADONE EXPOSURE PRODUCES PHYSICAL-DEPENDENCE AND ALTEREDBEHAVIORAL-DEVELOPMENT IN THE RAT

Pregnant rats were implanted with osmotic minipumps containing either methadone hydrochloride (9 mg/kg/day) or sterile water. Their offsprin g were cross-fostered so that the following prenatal/postnatal exposur e groups were obtained: water/ water, methadone/water, water/methadone and methadone/methadone. Methadone slightly reduced litter size, part icularly the number of male offspring, and reduced litter birth weight . The induction or maintenance of physical dependence in the postnatal methadone exposure groups was confirmed by an experiment in which PD1 9 pups were challenged with naloxone (1 mg/kg, s.c.). Methadone concen trations were assayed in pup brain on postnatal days 4, 10 and 22. Pos tnatal exposure to methadone via maternal milk produced measurable lev els of methadone. which decreased with age. Neuromuscular and physical development were assessed. Exposure to methadone accelerated acquisit ion of the righting reflex, but tended to delay the acquisition of the negative geotaxic response. Postnatal exposure to methadone was assoc iated with decreased somatic growth as measured through postnatal day 21. The older pups (postnatal day 21) exposed to methadone exhibited v ariations in activity levels: pups exposed to methadone both prenatall y and postnatally exhibited the least amount of spontaneous locomotor activity and pups exposed only postnatally exhibited the most activity . Therefore, it is possible to induce and/or maintain physical depende nce via lactation in rat pups fostered to methadone-treated dams. Peri natal exposure to methadone by this route produces several subtle disr uptions of pup development in the absence of grass maternal or fetal t oxicity.