Abstinence-dependent effects of long-access cocaine self-administration on nucleus accumbens astrocytes are observed in male, but not female rats

Abstract

Accumulating evidence indicates significant consequences for astrocytes associated with drug abuse. For example, reductions in structural features and synaptic colocalization of male rat nucleus accumbens (NAc) astrocytes are observed following short-access (ShA, 2 hours/day) self-administration and extinction from cocaine, methamphetamine, and heroin. However, it is unknown whether these observations extend to other rodent models of drug abuse, how enduring these effects may be, and whether similar effects are observed in female rats. Here we assess the effects of long-access (LgA, 6 hours/day) cocaine self-administration and abstinence on NAc astrocytes separately in male and female rats, a commonly used behavioral approach to investigate the incubation of cocaine craving. NAc astrocytes from male rats exhibit extensive ([~]40%) reductions in surface area, volume, and postsynaptic colocalization 45 days, but not 24 hours after the last self-administration session. In contrast, no effect of self-administration was observed in astrocytes from female rats. Moreover, no effect of LgA self-administration and abstinence was observed on NAc GLT-1 expression in female rats, an effect that has been well described in males. The results indicate striking and sexually dimorphic effects of abstinence subsequent to LgA self-administration on astrocytes. Taken together, these results indicate a pivotal role of prolonged abstinence in the effects of cocaine self-administration on NAc astrocytes, and extend a growing body of evidence regarding sex differences in the cellular consequences of drug self-administration in the brain.