Alcohol use disorder (AUD) is a debilitating pattern of chronic alcohol use affecting ten-percent of the U.S. population. Stress is a well-established trigger that exacerbates the physiological and psychological side effects of AUD, yet current pharmacological treatments of AUD do not sufficiently address the influence of stress on alcohol addictive behaviors.
Oxytocin (OXT), a neurotransmitter with established anti-anxiety effects, demonstrates promise for diminishing alcohol intake and relapse in rodents, yet currently has limited therapeutic value due to some of its side effects. Our research continues to probe the application of OXT for the treatment of AUD while also seeking to enhance its therapeutic profile via advanced drug delivery. One such mechanism, liposome encapsulation, may optimize the effects of OXT by increasing bioavailability and providing direct transportation of liposome-OXT to the brain.
To assess the potential therapeutic effect of OXT on stress-provoked alcohol-seeking behavior, we trained female Long-Evans rats to self-administer alcohol via lever pressing for 20% v/v ethanol during daily conditioning sessions in an operant behavioral chamber. After animals established stable responding, the animals' stress-induced motivation to seek and consume alcohol was evaluated. Administration of the pharmacological stressor yohimbine significantly enhanced ethanol responding. The increased alcohol use and seeking behavior demonstrated by our rats was diminished when OXT was co-administered with yohimbine. Importantly, co-administration of liposome-OXT and yohimbine optimized this effect.
These results demonstrate that systemic OXT and liposome-encapsulated OXT can attenuate stress-enhanced alcohol responding, with the enhanced formulation of liposome-OXT providing a greater therapeutic effect.