Evaluating oxytocin in opioid withdrawal: a translational study
As the opioid epidemic continues to spread in the United States, it’s important to discover new and more effective treatments. Using a preclinical model of opioid use disorder (OUD) in mice, we will investigate the ability of the hormone oxytocin to alleviate the physical opioid withdrawal symptoms, sleep dysregulation, and protracted affective behaviors.
Need/Problem: e are currently experiencing a global opioid epidemic; however, the prevalence of opioid use disorder (OUD) is especially visible in the US, where drug overdose is now the leading cause of accidental death. Individuals who are dependent on opioids continue to take these drugs despite the negative consequences to their lives and the risk of death. A major factor driving this persistent drug taking is because opioid withdrawal is both a physically and mentally traumatic experience. In addition, withdrawal from opioids can have long lasting effects on anxiety and sleep. Some of the best available pharmacotherapies for OUD, however, are other opioids. This replacement therapy prevents the trauma of withdrawal but maintains opioid dependence and has a high rate of relapse. Therefore, clinicians desperately need novel therapies to alleviate the physical, emotional, and sleep disturbing properties of opioid withdrawal.
Grant Summary: Using a preclinical model of OUD in mice, we will investigate the ability of the hormone oxytocin to alleviate the physical opioid withdrawal symptoms, sleep dysregulation, and protracted affective behaviors.
Goals and Projected Outcomes: This project will definitively inform us if oxytocin has efficacy across all 3 of the afore mentioned metrics for opioid withdrawal. It will also establish a preclinical pipeline of assays to investigate future compounds both within the oxytocin signaling pathway and targeting other potential biological mechanisms.
Dr. Zoe McElligott
Grant Details: Male and female mice will be exposed to either our 3-day morphine dependence paradigm, or will be saline controls (Luster and Cogan, et al., Addiction Biology, 2019). Prior to morphine withdrawal, half of the animals will be injected with oxytocin and half with vehicle. We will monitor somatic withdrawal signs (e.g. escape jumps, paw tremors, fecal boli production, etc.) and weight loss across all 3 days. Concurrently, and for 1 week following, we will monitor sleep behavior using the Piezo Sleep System. 6 weeks following the paradigm, using the same mice we will examine behavior in the elevated plus maze, the open-field, social interaction, and locomotor activation to challenge doses of morphine. This will afford us the ability to gauge how oxytocin alters both the acute and protracted withdrawal experience on an individual animal basis. Importantly, these studies will serve as an important preclinical condition, corresponding to the clinical study our colleagues Drs. Pedersen and Garbutt are simultaneously conducting.