Myelin plasticity is involved in several forms of learning in mice. Yalçın et al. now show that it also contributes to maladaptive opioid reward learning. They first showed that phasic optogenetic stimulation of dopamine (DA) neurons in the ventral tegmental area (VTA) increased the number of proliferating oligodendroglia precursor cells (OPCs) selectively in the VTA; this resulted in an increase in oligodendrocytes and enhanced myelination of VTA DA neurons. Morphine-induced reward conditioning similarly promoted VTA OPC proliferation and increased the number of oligodendrocytes wrapped around VTA DA axons. Blocking oligodendrogenesis or blocking BDNF–TrkB signalling — which is involved in neuronal-activity-regulated oligodendrogenesis — reduced morphine-associated place preference (a form of reward learning) without affecting preferences for social or sugar rewards. Moreover, it blunted the increase in DA levels in the nucleus accumbens that is normally observed when mice enter a chamber previously paired with morphine. As the effects were not mediated by κ-opioid receptors expressed on OPCs, these findings suggest that morphine-induced DA neuron activity drives myelination of these neurons and thereby promotes morphine-seeking behaviours.

Original reference: Nature https://doi.org/10.1038/s41586-024-07525-7 (2024).