Procedural separation of appetitive and consummatory behaviors in operant ethanol self-administration: A review and...

Despite decades of research, no new FDA-approved medications for alcohol use disorder (AUD) have emerged in over 25 years. Enhancing the translational relevance of preclinical models by more precisely capturing the behavioral and neurobiological features of AUD offers a promising path toward identifying novel therapeutic targets. Operant self-administration paradigms are essential for modeling voluntary ethanol intake in rodents, yet traditional approaches often confound appetitive (seeking) and consummatory (intake) behaviors. A biphasic sipper model developed by Hank Samson's laboratory addressed this limitation by allowing extended, uninterrupted access to ethanol following operant responding, enabling a clearer dissociation between seeking and consumption. In this review, we synthesize key findings from studies employing this methodology which investigated the behavioral and neurobiological mechanisms underlying alcohol use. We emphasize how over two decades of research employing this approach have demonstrated that ethanol-directed behaviors are dynamic processes, shaped by internal states, environmental cues, and prior experience. Finally, we introduce an open-source analytical framework in the R programming language designed to standardize the analysis of high-resolution temporal data generated by the biphasic sipper paradigm. Together, these methodological and analytical advances enhance the translational potential of preclinical models and may ultimately aid in the discovery of novel therapeutic targets for AUD.