Alcohol and nicotine vapor co-exposure differentially engages prelimbic prefrontal cortex activity and decreases anxiety-like behavior in rats

Alcohol and nicotine are two leading causes of preventable deaths in the United States. Simultaneous co-use of alcohol and nicotine is rising, as is the use of electronic nicotine delivery systems (ENDs). During early alcohol and nicotine co-use, users report decreased anxiety and increased feelings of pleasure. The prelimbic (PL) region of the medial prefrontal cortex (mPFC) is a target of alcohol- and nicotine-related plasticity. We investigated the consequences of acute, simultaneous alcohol and nicotine exposure on PL activity and anxiety-like behavior in female and male Sprague Dawley rats. We found that alcohol and nicotine alone or in combination increased PL neuron excitability in both females and males. Alcohol alone significantly decreased continuous evoked firing in females but not in males, and no changes were seen following nicotine alone or alcohol and nicotine in combination. In a separate experiment, immediately following acute alcohol/nicotine, alcohol/PGVG, or air vapor exposure, rats went through the novelty suppressed feeding assay. Though no differences were seen in latency to initiate feeding, females exposed to alcohol and nicotine spent more time in center compared to air/air and EtOH/PGVG controls and males exposed to ethanol and nicotine spent more time in center than air/air controls only. Females and males had decreased PL cFos activation following alcohol and nicotine vapor exposure compared to air/air controls. Together, these data suggest that alcohol and nicotine co-exposure differentially affect PL activity and anxiety-like behavior, potentially contributing to alcohol and nicotine co-use addiction pathology.