Association for Behavior Analysis International

The opioid landscape has recently shifted to include xylazine, a veterinary anesthetic, as an adulterant in the illicit fentanyl supply. The health impacts of xylazine as an emerging fentanyl adulterant has raised alarm, warranting research on the impacts of xylazine on fentanyl’s behavioral and biological effects. Thus, we evaluated the effects of xylazine on fentanyl demand and withdrawal as compared to the FDA-approved opioid withdrawal medication, lofexidine (Lucemyra®). This is important because lofexidine and xylazine are both adrenergic α2a agonists, however, lofexidine is not a noted fentanyl adulterant. Using a rodent self-administration model, we evaluated the effects of xylazine or lofexidine on fentanyl demand, body weight, and withdrawal. Evaluations of effects as a function of sex as a biological variable was important because clinical experiences indicate that women experience more severe fentanyl withdrawal symptomatology compared to men, and we have previously shown that females are more susceptible to withdrawal compared to males. We next evaluated body weight changes and determined that body weight loss may be an important translational indicator of withdrawal severity from xylazine and fentanyl. Finally, we evaluated gastrointestinal consequences of xylazine/fentanyl co-use to determine if fentanyl pharmacokinetics can be therapeutically targeted to reduce withdrawal severity.

Intermediate

Dr. Cassandra Gipson-Reichardt is a tenured Associate Professor in the Department of Pharmacology and Nutritional Sciences at the University of Kentucky. She is currently the Program Chair-Elect for the College on Problems of Drug Dependence and the President-Elect for Division 28 of the American Psychological Association. Her research program focuses on elucidating neurobehavioral mechanisms underlying substance use by leveraging preclinical rodent models, focusing on translation of clinical substances use patterns. From these efforts, Dr. Gipson-Reichardt developed the first intravenous self-administration model of xylazine/fentanyl co-use in rats, deriving aspects of the model directly from surveillance signals from the illicit drug supply. Her lab studies neurobehavioral underpinnings of addiction, focusing on factors that impact glutamatergic and dopaminergic signaling and neural circuit adaptations during drug use, including endogenously cycling and synthetic contraceptive hormones as well as neuroimmune dysfunction within the brain reward pathway. Her lab also focuses on nicotine self-administration as well as polysubstance use involving opioids and psychostimulants and ethanol and nicotine.