Chen : Sex-dependent Effects of Alcohol and Oxycodone Polysubstance Use
Sex-dependent Effects of Alcohol and Oxycodone Polysubstance Use
Yueyi Chen1, Salvador Huitron Resendiz2, Amanda Roberts2, Adam Kimbrough1
1. Purdue University, Department of Basic Medical Sciences, West Lafayette, IN, USA
2. The Scripps Research Institute, Animal Models Core, La Jolla, CA, USA
This study aimed to investigate concurrent polysubstance use disorder (PUD) by designing two preclinical models involving alcohol and oxycodone. We hypothesized that withdrawal from one substance would lead to increased intake of the other.
To study alcohol withdrawal on oxycodone self-administration, mice were exposed to chronic intermittent ethanol vapor to induce alcohol dependence, while a control group remained alcohol naïve. Both groups experienced two weeks of intravenous oxycodone self-administration sessions during alcohol withdrawal of mice experienced CIE.
To study oxycodone withdrawal on alcohol intakes, mice were made oxycodone-dependent through i.p. injections, while a control group received saline injections. During oxycodone withdrawal, the mice had access to alcohol and water for 2-hour drinking sessions.
The results from the first study showed a significant increase in oxycodone self-administration during the last three sessions in male mice from the alcohol withdrawal group compared to control group. However, female mice did not exhibit the same increase. In the second study, female mice injected with oxycodone showed a significant increase in alcohol intake compared to the control group. However, male mice did not demonstrate the same effect.
These findings establish preclinical models of concurrent alcohol and oxycodone use in mice. Interestingly, the effects of withdrawal and substance modulation differed between males and females. Males appeared to be more sensitive to alcohol withdrawal’s influence on oxycodone intake, while females showed greater sensitivity to oxycodone withdrawal’s impact on alcohol consumption.