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The perinatal opioid syndrome has been recognized for over a century. Examination of this phenomena has revealed no pathognomonic symptoms, but rather a constellation of somatic and neurobiological deficits that may continue into adulthood. Research in this area has found that exogenous opioids such as heroin and methadone interact with opioid receptors and influence development. Moreover, a fundamental and important observation shows that endogenous opioid peptides, the counterpart to exogenous opioids, normally modulate developmental events. Opioids are inhibitory growth factors that tonically mediate their action by way of the opioid receptor. Studies now reveal that [Met5]-enkephalin, a naturally occurring neuropeptide derived from proenkephalin A, is the most potent opioid peptide in regulating growth and acts on a newly discovered opioid receptor-the zeta (f) receptor. Cell proliferation appears to be the major target of growth-related opioids. Exogenous opioids such as methadone and heroin also have an affinity for the zeta receptor, and involvement of these compounds with growth can be envisioned. Continued study of endogenous opioid systems and developmental processes, particularly at the cell and molecular level, may permit elucidation of the etiology and pathogenesis of various abnormalities (e.g., mental retardation, tumorigenesis) associated with neural development.
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Ian S. Zagon, Ph.D. and Patricia J. McLaughlin, Ph.D.
Ian S. Zagon and Patricia J. McLaughlin are with the Department of Anatomy, Pennsylvania State University College of Medicine, P.O. Box 850, Hershey, PA 17033. Address correspondence to Professor Zagon. This review was prepared under NIH grants NS-20500 and NS-20623.