Rapid appearance of negative emotion during oral fentanyl self-administration in male and female rats.

The United States opioid epidemic is defined by rampant and treatment resistant fentanyl use. Better understanding of neural substrates underlying this phenomenon is essential to slowing the opioid crisis. Intravenous and vapor self-administration (SA) are the standard models for studying fentanyl use in rodents, however they many carry pragmatic downsides. Here, we used a novel oral fentanyl self-administration model that provides key translational and technical benefits and can be readily applied in other labs to study the neurobiology of fentanyl SA. This method captured individual and sex differences necessary for studying substance use risk propensity and uncovered a rapid shift in affective state in rats, suggesting and shift from positive to negative reinforcement within each fentanyl taking session.