Chronic Alcohol Drinking Drives Sex-Specific Differences in Affective Behavior and Medial Prefrontal Cortex Activity in CRF1:Cre:tdTomato Transgenic Rats

In 2021, 131 million adult Americans reported drinking alcohol in the last month, despite the well-known consequen-ces of alcohol consumption. While alcohol use disorders (AUDs) are associated with both mood and chronic pain dis-orders, the relationship between alcohol drinking and affective and nociceptive behaviors remains unclear. Corticotropin releasing factor receptor-1 (CRF1) has been implicated in alcohol drinking, affective states, and pain sen-sitivity, often in a sex-dependent manner. In order to probe the effects of alcohol drinking on activity of CRF1+ cells and to also test the hypothesis that alcohol drinking is associated with both basal and subsequent affective and noci-ceptive readouts, we put male and female CRF1:cre:tdTomato rats through a battery of behavioral tests before and after intermittent access to alcohol. Following baseline testing, rats began alcohol (or water) drinking. Females con-sumed more alcohol in the first week, but there was no effect of sex on overall alcohol intake. Following three to four weeks of drinking, behavioral tests were repeated. Alcohol drinking decreased mechanical sensitivity, but no other effects of alcohol drinking were observed between experimental groups. Individual alcohol intake correlated with affec-tive behavior in both sexes but only correlated with thermal sensitivity in males. There were no main effects of alcohol drinking or sex on CRF1+ neuronal activity in the medial prefrontal cortex (PFC) but final session alcohol intake corre-lated with activity in CRF1+ neurons in the infralimbic (IL) subregion. Together, our results suggest complex interplay between affective state, alcohol drinking, and the role of prefrontal CRF1+ neurons in mediating these behaviors.

Automated summary

Despite the well-known consequences of alcohol consumption, a large number of adult Americans reported drinking alcohol in 2021, with no clear understanding of the relationship between alcohol drinking and affective and nociceptive behaviors. This study explored the effects of alcohol drinking on CRF1+ cells and found a complex interplay between alcohol drinking, affective state, and the role of prefrontal CRF1+ neurons in mediating these behaviors. The results showed that alcohol drinking decreased mechanical sensitivity and correlated with affe-ctive behavior, suggesting the involvement of CRF1 in these processes.