Doris I. Olekanma ¹, Sonia A. Cavigelli ^1,2, Helen M. Kamens ^1,2
1 Huck Institute of Life Sciences, Neuroscience, Pennsylvania State University
² Department of Biobehavioral Health, Pennsylvania State University

Opioid Use Disorder remains an unrelenting public health concern in the United States, with hundreds of overdose deaths occurring daily. Clinical data suggest that women may be more susceptible to the addictive properties of opioids than men. Although adolescent stress is a risk factor for later use, it remains unclear whether biological sex moderates vulnerability to stress-induced increases in opioid use. To address this gap, we investigated how sex and genetic background influence the effects of adolescent stress on opioid intake. Male and female C57BL/6J and BALB/cJ mice were exposed to repeated restraint stress (2 h/day for 14 days; PND 37 – 50) or control conditions. Body weight was measured daily, and blood corticosterone was obtained at the end of the final restraint session. In adulthood (PND 60), morphine consumption was examined using a two-bottle choice protocol. Repeated daily restraint in adolescence was an effective stressor, as evidenced by delayed body weight gain and elevated corticosterone levels, even after 14 exposures, in both strains and sexes. Adolescent stress selectively increased morphine consumption in female C57BL/6J mice compared to controls, with no significant effects observed in male C57BL/6J or BALB/cJ mice. Our findings highlight how adolescent stress can alter future intake of opioids in a strain and sex specific manner, supporting gene X environment contributions to Opioid Use Disorder.