Automated Operant Intermittent Alcohol Drinking In Socially-Housed Mice via The Intellicage Testing System

Despite known confounds of social isolation on rodent behavior, many investigators rely on singly housing mice to assess alcohol preference in preclinical models of alcohol use disorder (AUD). This protocol describes a social alcohol drinking task that allows for high-throughput, automated assessment of alcohol drinking behaviors in mice without the confounding impacts of stress induced by social isolation. The IntelliCage testing system enables investigators to simultaneously assess operant alcohol drinking behavior in up to 16 same-sex mice, each uniquely identified with a subcutaneously implanted radiofrequency identification (RFID) transponder. Access to sipper bottles is software-controlled and can be adjusted individually for each mouse. In this chronic, intermittent alcohol drinking paradigm, mice voluntarily engage in operant nosepokes to access sipper bottles containing 20% alcohol for six consecutive weeks. Alcohol bottles are only accessible every other day for 24 h at a time and can be optionally adulterated with quinine to assess punishment-insensitive drinking. Visits to each operant corner, nosepokes, and lick data are automatically recorded for each mouse. Detailed experimental methods and the open-source code to analyze the recorded data will allow investigators to assess alcohol drinking behaviors relevant to AUD in an increasingly efficient and ethologically relevant manner.