Endogenous Opioids and Prenatal Determinants of Neuroplasticity

Abstract

An endogenous opioid system involved in the growth of developing, neoplastic, renewing, and healing cells and tissues was first postulated in the early 1980’s. This concept arose from the demonstration that blockade of native opioids (i.e., enkephalins, endorphins) from opioid receptors in developing animals (Zagon and McLaughlin, 1983a,c) or tumors transplanted into mice (1983b) accelerated growth when the opioid antagonist utilized was continuously available. Such observations gave rise to the hypothesis that endogenous opioids serve as growth inhibitory molecules and function in an active, tonic fashion. At this time it also was learned that if opioids were disrupted from opioid receptors for only a short time each day, growth could be delayed. The explanation for this latter observation resided in knowledge that during the time of opioid receptor blockade there is a compensatory production of opioid peptides and receptors. During the interval when the opioid antagonist is not available, an increased concentration of peptide can interact with cells containing more receptors, and the functional sensitivity is heightened. Since opioids are growth inhibitory, the finding of suppression of development or oncogenesis was in keeping with this thesis. These defining principles set forth the hypothesis that native opioid peptides are associated with growth, in addition to the function of opioids/opioid receptors in neuromodulatory events (Akil et al., 1984).