The Garden of pDYN: The impact of pDYN gene deletion on ethanol self-administration and reinforcement in female mice

Debilitating over-consumption of alcohol, often culminating into a prevalent psychiatric disorder known as alcohol use disorder (AUD), stands as one of the United States’ most expensive societal battles to face (Harwood et al., 1998). Consequently, the public’s desire and scientists’ motivation to develop novel pharmacological solutions to treat it is high. Recent and ongoing research presents new insights into the role of the dynorphin/kappa opioid receptor (DYN/KOR) system as an inhibitor of dopamine release and a regulator of the negative affective states that come with alcohol withdrawal (Karkhanis et al., 2017). However, this growing body of literature is predominantly conducted using male subjects, highlighting a sex-related gap in our knowledge of the DYN/KOR system in females. As such, we focused our current study to investigate the influence of the deletion of the gene encoding for prodynorphin (pDYN) in alcohol reinforcement and self-administration in female mice. We utilized an operant conditioning paradigm, an established model of drug self-administration/reinforcement (Guttlein et al., 2021). At the start of our experiment, we consistently used a fixed ratio (FR1) reinforcement schedule, testing different ethanol concentrations (2%, 4%, and 8%). Afterwards, we stayed at 8% ethanol, but transitioned to a fixed ratio (FR3) schedule before incrementally increasing our schedule by 3 (FR6 and FR9). However, we did not observe any significant changes in alcohol intake or active lever presses using the FR1 or the progressive ratio of three schedules of reinforcements between mice lacking the pDYN gene and their wildtype controls, suggesting that the pDYN gene deletion did not impact alcohol self-administration or reinforcement in female mice.