Abstract
The endogenous opioid system, comprised of multiple opioid neuropeptide and receptor gene families, is highly expressed by developing neural cells and can significantly influence neuronal and glial maturation. In many central nervous system (CNS) regions, the expression of opioid peptides and receptors occurs only transiently during development, effectively disappearing with subsequent maturation only to reemerge under pathologic conditions, such as with inflammation or injury. Opiate drugs with abuse liability act to modify growth and development by mimicking the actions of endogenous opioids. Although typically mediated by μ-opioid receptors, opiate drugs can also act through δ- and κ-opioid receptors to modulate growth in a cell-type, region-specific, and developmentally regulated manner. Opioids act as biological response modifiers and their actions are highly contextual, plastic, modifiable, and influenced by other physiological processes or pathophysiological conditions, such as neuro-acquired immunodeficiency syndrome. To date, most studies have considered the acute effects of opiates on cellular maturation. For example, activating opioid receptors typically results in acute growth inhibition in both neurons and glia. However, with sustained opioid exposure, compensatory factors become operative, a concept that has been largely overlooked during CNS maturation. Accordingly, this article surveys prior studies on the effects of opiates on CNS maturation, and also suggests new directions for future research in this area. Identifying the cellular and molecular mechanisms underlying the adaptive responses to chronic opiate exposure (e.g., tolerance) during maturation is crucial toward understanding the consequences of perinatal opiate exposure on the CNS.
Highlights
Maternal opiate abuse and neonatal abstinence syndrome are increasing at an alarming rate and this is in large part fueled by increases in the illicit use of prescription opiates [1,2,3,4]
It was well established in the 1970s that in utero and perinatal exposure to opiate drugs would hinder brain maturation, not until the early 1990s was it realized that opiates per se, through direct actions on opioid receptor-expressing immature neurons and glia, could intrinsically affect the maturation of the central nervous system (CNS)
Opioid receptors are expressed by the neural progenitor cells (NPCs) that are the common precursors of all CNS neurons and macroglia, inferring that opioids per se might directly influence very early lineage and fate decisions via paracrine or autocrine feedback loops
Summary
Maternal opiate abuse and neonatal abstinence syndrome are increasing at an alarming rate and this is in large part fueled by increases in the illicit use of prescription opiates [1,2,3,4]. The goal of this review is to examine our current understanding of the direct cellular and molecular effects of opiates on central nervous system (CNS) maturation It was well established in the 1970s that in utero and perinatal exposure to opiate drugs would hinder brain maturation, not until the early 1990s was it realized that opiates per se, through direct actions on opioid receptor-expressing immature neurons and glia, could intrinsically affect the maturation of the CNS.
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