Development of central and peripheral catecholaminergic systems in rats addicted perinatally to methadone.

Abstract

In order to examine the effects of perinatal methadone exposure on development of central and peripheral catecholaminergic systems, methadone was administered daily to pregnant and nursing rats; the effects on postnatal development of body and brain weights, adrenal catecholamine (CA) levels and adrenal activities of the CA biosynthetic enzymes, tyrosine hydroxylase (TH) and dopamine β-hydroxylase (DBH) were measured along with brain TH. In general, pups whose mothers received methadone exhibited deficits in adrenal CA and TH; however, the adrenal effects in pups born to methadone-treated mothers but reared by controls (prenatal exposure only) were less pronounced than in those born to and reared by addicted mothers (prenatal + postnatal exposure), and the greatest disturbances were found in pups born to controls but reared by drug-treated mothers (postnatal exposure). These data suggest that methadone exposure in utero protects the neonate from the postnatal slowing of adrenomedullary development caused by subsequent maternal drug treatment. In contrast, the prenatal period of exposure appeard to sensitize the pups to the lag in brain TH development resulting from subsequent postnatal treatment, since a greater effect was seen in those exposed prenatally + postnatally than in those exposed only prenatally or only postnatally. The adrenal results obtained with maternal administration differed from those after direct injections of pups with methadone, suggesting that drug-induced alterations in maternal behaviour and/or metabolism may play a role in the peripheral neurochemical deficits in the pups; similarly, direct neonatal methadone treatment produced reductions in brain TH but postnatal exposure via maternal administration did not. These data indicate that fetal or neonatal exposure to methadone changes the neurochemical development of catecholaminergic systems in both central and peripheral nervous tissues; the magnitude and type of alteration depend upon both the time period and route of exposure.