PERINATAL EXPOSURE TO METHADONE AFFECTS CENTRAL CHOLINERGIC ACTIVITY IN THE WEANLING RAT

Pregnant rats were implanted with osmotic minipumps containing either methadone hydrochloride (initial dose, 9 mg/kg/day) or sterile water. Their offspring were cross-fostered so that they were exposed to metha done prenatally and/or postnatally. Perinatal methadone exposure disru pted cholinergic activity on postnatal day 21 as measured by the turno ver rate of acetylcholine (TR(ACh)) in both female and male rats, alth ough there were some sexually-dimorphic responses. The most profoundly affected brain region was the striatum, where prenatal exposure to me thadone increased ACh turnover, whether or not the rats continued to b e exposed to methadone postnatally. It appears unlikely that neonatal withdrawal contributes to brain regional changes in ACh turnover, as c ontinued postnatal exposure to methadone did not prevent the prenatal methadone induced changes.