UC San Diego

Chronic intermittent ethanol vapor exposure (CIE) produces dependence, alters the structure of pyramidal neurons, and decreases oligodendroglial progenitors in the medial prefrontal cortex (mPFC). The effect of early abstinence from CIE on these neuroadaptations are unclear and unknown and were investigated. Adult male Wistar rats were exposed to CIE for 7 weeks, after which they underwent 3 days of abstinence. On the 4th day, CIE abstinent and age matched CIE naïve controls experienced trace fear conditioning (TFC) to determine the effect of early abstinence on neuroadaptations in the mPFC and retrieval of emotional memories, and the interactions between TFC and abstinence-induced neuroadaptations in the mPFC. To assess neuroadaptations, mPFC tissue was processed for Western blotting, immunohistochemistry and Golgi-Cox staining. CIE abstinent animals froze less during retrieval, indicating deficits in memory functions dependent on the mPFC. Abstinence enhanced dendritic complexity of layer 2/3 mPFC pyramidal neurons, as did trace fear conditioning. However, trace fear conditioning combined with CIE had no additive effect. Additionally, abstinence altered plasticity-related proteins in mPFC (increased total NR2A expression and decreased PSD-95) and TFC did not affect these adaptations. However, TFC produced profound alterations in oligodendroglial proteins (increases in transcription factor Olig2 and myelin basic protein (MBP)) and abstinence abolished these effects. Our findings indicate that neuroadaptations in the mPFC persist into early abstinence in CIE animals, and these deficits are associated with reduced memory functions dependent on the PFC