Prenatal levo-alpha-acetylmethadol (LAAM) and/or naloxone: effects on brain chemistry and postweaning behavior

Female rats were treated daily with water or 0.2 mg LAAM/kg (PO) beginning 3 weeks before mating and continuing until parturition, after which addicted neonates were allowed to withdraw spontaneously. Beginning on the 14th day of gestation half of the animals in each group were injected (SC) 4 and 2 hours earlier with naloxone (Nx, 1 or 5 mg/kg) and the others with saline. Treatment with LAAM retarded maternal weight gain prior to mating but not during gestation. Evidence of dependence in the LAAM treated dams was manifest as a transient but robust weight loss following each dose of Nx. Offspring exposed to LAAM whose mothers were injected with Nx demonstrated significant perinatal mortality but survivors showed no evidence of growth retardation or biochemical and behavioral dysfunction. Pups exposed only to LAAM and withdrawn after birth showed some evidence of congenital effects. These include (1) lower 21 day postnatal body weights, (2) lower 1 and 3 day postnatal brain weights, (3) lower 19 day fetal brain protein concentrations, (4) lower 1 day postnatal brain DNA, RNA and protein content, and (5) lower levels of unconditioned exploratory activity at 1 1/2 and 10 months of age. The effects on growth and brain weight and biochemical parameters were transient, since control values were attained by 21 or 45 days of age. The absence of these effects in subjects exposed to both LAAM and Nx is interpreted as a screening effect of in utero withdrawal, with only the most resistant subjects surviving to be tested, the result of less severe spontaneous withdrawal because of displacement of cumulated LAAM metabolites by Nx or habituation to postnatal withdrawal stress by precipitated in utero withdrawal.