Critical Role of Accumbal Oligodendrocytes in Cocaine Seeking

초록

Numerous studies have demonstrated various changes caused by chronic cocaine exposure in mice. While demyelination is known to be one of the consequences of cocaine use, the impact of cocaine on oligodendrocytes has yet to be determined. In the present study, we investigated neurobiological dynamics induced by chronic cocaine exposure, specifically focusing on 1) structural changes, 2) oligodendrocyte dysfunction, and 3) methods and effects of recovery. Initially, we observed that mice injected with cocaine for 5 days showed sensitization to cocaine after a 3-week withdrawal period. These mice demonstrated significant alterations in the thickness of myelin sheath and the expression levels of various oligodendrocyte-related genes, which are related to the oligodendrocyte maturation stage. To restore the myelin sheath, which is reduced by chronic cocaine exposure, we employed miconazole drug injection or viral injection of myelin basic protein (MBP) overexpression. Consequently, remyelination was able to restore mRNA levels of oligodendrocyte-related genes and inhibit cocaine-seeking behaviors. Collectively, our findings suggest that cocaine exposure induces functional impairment of oligodendrocytes, which could affect neuronal transmission. These results can provide a foundation for understanding the causal relationship between oligodendrocytes and neurons affected by cocaine, highlighting a potential target for ameliorating cocaine-induced deficits