Early clinical reports of severe morbidity and mortality in infants born passively addicted to opiates are being reinterpreted in light of recent reports of an improved prognosis in children born to women on methadone maintenance programs who avail themselves of antenatal and well-baby clinics, and in whom illicit polydrug abuse and poor nutrition are kept to a minimum (Finnegan, 1978, 1983). Most of the preclinical animal literature dealing with effects of methadone during development would suggest that methadone should never have been released for clinical use by people of childbearing age or who are pregnant. However, we believe that there are many flaws in the design and interpretation of these experiments and have completed or are in the process of extending a series of experiments with the opiate 1-alpha-acetylmethadol (LAAM) or its active metabolites in which we can duplicate many effects reported for methadone but which appear to be preventable or nonexistent, if careful attention is paid to animal modeling and potential epiphenomena. We propose to continue these studies as well as incorporate several new studies to determine the relevance (i.e. generality or specificity) of our observations with LAAM, to study the consequences of hypoxia and hypercapnia equivalent to that produced by (acutely toxic) doses of methadone typically used by other laboratories for such studies, to directly test the importance of opiate-type withdrawal, to study the interactive effects of neonatal opiate-type withdrawal with a model of maternal neglect engendered by rearing pups in large litters of 24, and to use biochemical, endocrinological and functional (e.g. behavioral) data derived from our studies to determine the possible mechanisms whereby exposure to opiates imparts the sundry congenital effects which have bean reported.
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