Anterior insula activity during alcohol and social reward self-administration and choice in male and female rats.

Alcohol use disorder (AUD) is characterized by the prioritization of alcohol over healthier non-alcohol rewards, posing significant challenges for addiction treatment. Understanding the neural mechanisms driving this maladaptive preference is crucial for effective intervention. We previously showed that rats will choose alcohol over social reward in a discrete-choice task. Here, we used fiber photometry to investigate how anterior insula cortex (aIC) activity relates to choice and employed Linear Ballistic Accumulator (LBA) modelling to dissect the underlying decision processes. Male and female rats, transfected with calcium indicator jGCaMP7f in aIC, were trained to lever-press for either social reward or alcohol (20% ethanol) in alternating sessions, followed by discrete-choice sessions, and then punishment of alcohol choices. Rats developed a preference for alcohol over social reward, which was reversed when alcohol choices were punished. Model output successfully described this behaviour with the model-derived 'decision bias' tracking preference across all phases. Photometry recordings showed that, as alcohol preference emerged, increased aIC activity during the cue period preceding alcohol choices (relative to social choices) was significantly correlated with decision bias towards alcohol. During punishment, aIC activity bias was no longer related to decision bias, despite the preference shift. These results demonstrate that aIC activity is linked to alcohol reward and choice and suggest that aIC contributes to alcohol preference by encoding a bias in the evidence accumulation process. This highlights a specific role of aIC in the cognitive mechanisms of alcohol-seeking, and its potential as a target for therapeutic interventions.<b>Significance Statement</b> Understanding the neural basis of prioritizing alcohol over natural rewards is critical for combating alcohol use disorder. This study investigates how anterior insula cortex (aIC) activity in rats relates to choices between alcohol and social reward. Using fiber photometry and cognitive modelling, we found that aIC activity is not only consistently higher for alcohol-related actions but also, during the decision period prior to choice. Differential activity for alcohol versus social choices significantly correlates with a model-derived "decision bias", the speed of evidence accumulation, favouring alcohol, once preference is established. This provides novel mechanistic insight, suggesting aIC contributes to alcohol preference by encoding a bias in the decision-making process, highlighting its role in alcohol seeking and as a potential therapeutic target.