Author:
Henricks Angela M.,Sullivan Emily D.K.,Dwiel Lucas L.,Keus Karina M.,Adner Ethan D.,Green Alan I.,Doucette Wilder T.
Abstract
AbstractBackgroundAlthough male and female rats differ in their patterns of alcohol use, little is known regarding the neural circuit activity that underlies these differences in behavior. The current study used a machine learning approach to characterize sex differences in local field potential (LFP) oscillations that may relate to sex differences in alcohol drinking behavior.MethodsLFP oscillations were recorded from the nucleus accumbens shell and the rodent medial prefrontal cortex of adult male and female Sprague-Dawley rats. Recordings occurred before rats were exposed to alcohol (n=10/sex X 2 recordings/rat) and during sessions of limited access to alcohol (n=5/sex X 5 recordings/rat). Oscillations were also recorded from each female rat in each phase of estrous prior to alcohol exposure. Using machine-learning, we built predictive models to classify rats based on: 1) biological sex; 2) phase of estrous; and 3) alcohol intake levels. We evaluated model performance from real data by comparing it to the performance of models built and tested on permutations of the data.ResultsOur data demonstrate that corticostriatal oscillations were able to predict alcohol intake levels in males (p<0.01), but not in females (p=0.45). The accuracies of models predicting biological sex and phase of estrous were related to fluctuations observed in alcohol drinking levels; females in diestrus drank more alcohol than males (p=0.052), and the male vs. diestrus female model had the highest accuracy (71.01%) compared to chance estimates.Conversely, females in estrus drank similar amounts of alcohol to males (p=0.702), and the male vs. estrus female model had the lowest accuracy (56.14%) compared to chance estimates.ConclusionsThe current data demonstrate that oscillations recorded from corticostriatal circuits contain significant information regarding alcohol drinking in males, but not alcohol drinking in females. Future work will focus on identifying where to record LFP oscillations in order to predict alcohol drinking in females, which may help elucidate sex-specific neural targets for future therapeutic development.
Publisher
Cold Spring Harbor Laboratory
Reference44 articles.
1. World Health Organization. Global status report on alcohol and health 2018. 2018. 450 p.
2. Sex and gender-related differences in alcohol use and its consequences: Contemporary knowledge and future research considerations;Drug Alcohol Depend [Internet],2015
3. Burden of disease associated with alcohol use disorders in the United States;Alcohol Clin Exp Res [Internet],2014
4. Sex differences, gender and addiction;J Neurosci Res [Internet],2017