The incubation of cocaine craving is dissociated from changes in glial cell markers within prefrontal cortex and nucleus accumbens of rats

Abstract

• Extended-access cocaine self-administration elicits an incubation of cocaine-seeking behavior during protracted withdrawal. • Extended-access cocaine self-administration lowers ventromedial prefrontal cortex expression of several glial cell markers in early withdrawal that persist into protracted withdrawal. • Extended-access cocaine self-administration produces few effects upon the expression of glial cell markers in the dorsomedial prefrontal cortex, or nucleus accumbens subregions. The majority of neurobiological research on cocaine addiction has centered on neuronal pathology, ignoring the fact that glial cells are critical contributors to brain function. The present study examined the expression of various glial cell subtype-specific proteins within forebrain regions that exhibit functional anomalies in addiction. For this, immunoblotting was conducted for a variety of markers of astrocytes and oligodendrocytes within prefrontal cortex (PFC) and nucleus accumbens (NAC) subregions of cocaine-abstinent rats (3 or 30 days). Cocaine-experienced rats exhibited a time-dependent increase in cocaine craving. Within ventral PFC, cocaine-experienced rats exhibited reduced expression of myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), and the NG2(+) proteoglycan that persisted into protracted withdrawal. Within the NAC core, a persistent reduction in Cx43 expression was also observed. No statistically significant protein changes were observed for the dPFC or the NAC shell. Thus, although a history of extended cocaine-access induced an incubation of cocaine craving, the observed changes in our glial-specific markers were time-independent during withdrawal. These data from rat are consistent with imagining and post-mortem findings from humans, indicating perturbations in oligodendrocyte function in those with cocaine use disorder. As myelin is critical for normal neuronal functioning and survival, the present data suggest a reduction in the functional integrity of oligodendrocytes as a potential mechanism underpinning the enduring PFC hypofunction reported in cocaine use disorder.