Endogenous and exogenous opioid effects on oligodendrocyte biology and developmental brain myelination

The elevated presence of opioid receptors and their ligands throughout the developing brain points to the existence of maturational functions of the endogenous opioid system that still remain poorly understood. The alarmingly increasing rates of opioid use and abuse underscore the urgent need for clear identification of those functions and the cellular bases and molecular mechanisms underlying their physiological roles under normal and pathological conditions. This review is focused on current knowledge on the direct and indirect regulatory roles that opioids may have on oligodendrocyte development and their generation of myelin, a complex insulating membrane that not only facilitates rapid impulse conduction but also participates in mechanisms of brain plasticity and adaptation. Information is examined in relation to the importance of endogenous opioid function, as well as direct and indirect effects of opioid analogues, which like methadone and buprenorphine are used in medication-assisted therapies for opioid addiction during pregnancy and pharmacotherapy in neonatal abstinence syndrome. Potential opioid effects are also discussed regarding late myelination of the brain prefrontal cortex in adolescents and young adults. Such knowledge is fundamental for the design of safer pharmacological interventions for opioid abuse, minimizing deleterious effects in the developing nervous system.