Search

We have used the developing chicken to determine if ornithine decarboxylase (ODC) activity is altered in fetuses chronically exposed to the opiate N-desmethyl-l-alpha-acetylmethadol (NLAAM) or rendered abstinent by acute injection of naloxone (Nx). Exposure to NLAAM from day 3 of embryogenesis did not significantly change brain ODC activity in 15, 17 or 19-day-old fetuses. Acute treatment of 17-day-old fetuses with a motility suppressant dose of NLAAM did not differentially affect ODC activity in NLAAM-dependent fetuses, but an additional treatment with Nx, which precipitated withdrawal, resulted in a significant increase in ODC activity in this group. We conclude that withdrawal can alter fetal ODC activity which otherwise appears normal, even though fetuses have been chronically exposed to and dependent upon an opiate.

Injection of l-alpha-noracetylmethadol (NLAAM), the active des-methyl metabolite of l-alpha-acetylmethadol, into chicken eggs on the 3rd day of embryonic development produced no deficits in body or brain weight, or brain nucleic acid and protein content in the 20-day check embryo. NLAAM decreased embryo viability in a dose-dependent manner as early as day 4. At this time measureable levels of radiolabeled NLAAM could be detected in the embryo; further sampling of whole embryos or embryo brains demonstrated continual exposure to NLAAM throughout development. The present report describes the utility of an avian model in studying the direct effects of prenatal opiate exposure on development.

Fetal chicks were made opiate-dependent by injections of N-desmethyl-1-alpha-acetylmethadol into the chorioallantois on day 3 of embryogenesis. The injections had no effect on subsequent hatchability; however, spontaneous fetal motility was significantly depressed. Injection of naloxone caused a significant increase in the motility of the opiate-exposed fetuses but had no effect on control fetuses. That naloxone's effect was an expression of opiate withdrawal and not due to antagonism of depressed motility is also supported by the observation that naloxone significantly reduced the hatchability of opiate-exposed chicks and not of control chicks. Thus the withdrawal of a developing organism from a narcotic may be more deleterious to its survival than continued exposure.