Effects of prenatal methadone on rat brain catecholamines

Methadone, injected subcutaneously into Wistar rats during the last trimester of gestation, significantly retarded offspring body and brain growth and the ontogeny of brain catecholamines. On postnatal days 1 and 20, the endogenous content and high affinity uptake of norepinephrine and dopamine were significantly lower in the forebrains of methadone-treated pups than in those of saline or pair-fed control offspring. On day 40, regional norepinephrine levels and uptake were similar in the brains of all three groups. However, the striata of methadone pups remained significantly lower in dopamine content and uptake than did those of saline pups at this age. Hindbrain norepinephrine and dopamine were not altered at any time point. These data indicate that prenatal exposure to methadone more severely retarded body and brain growth than did prenatal undernutrition alone. Furthermore, biochemical indices of the maturation of central catecholamine pathways suggest that prenatal methadone may retard catecholaminergic axonal growth from the hindbrain to the forebrain in rats.