Adolescent ethanol exposure produces sex-dependent modulation of ethanol-induced analgesia and cell type-specific vlPAG activation
Document Type
Article
Publication Date
5-16-2026
Publication Title
Alcohol
Abstract
Alcohol is commonly reported to produce analgesic effects, yet the mechanisms underlying alcohol-induced analgesia and the long-term impact of adolescent alcohol exposure on pain processing remain poorly understood. The present study examined whether a history of adolescent alcohol exposure alters ethanol-induced analgesic responses in adulthood and whether these effects are associated with changes in neuronal activation within the ventrolateral periaqueductal gray (vlPAG). Male and female mice were exposed to adolescent intermittent ethanol (AIE) vapor or air, followed by longitudinal assessment of mechanical sensitivity using the von Frey test during abstinence. In adulthood, mice received acute intragastric ethanol, and mechanical withdrawal thresholds were reassessed. Neural activation of mu-opioid receptor- and kappa-opioid receptor (KOR)-expressing vlPAG neurons was quantified using RNAscope in situ hybridization. Mice with a history of AIE exhibited persistent mechanical hypersensitivity during abstinence. Acute ethanol produced dose-dependent analgesia across sexes. Follow-up analyses revealed that AIE exposure selectively modulated ethanol responsiveness in females. Higher ethanol doses increased withdrawal thresholds in both air and AIE females, whereas an intermediate dose produced analgesic effects only in AIE females. Notably, at a low ethanol dose that did not significantly alter mechanical sensitivity in males, AIE females exhibited higher withdrawal thresholds than air controls, accompanied by reduced activation of KOR-expressing neurons in the vlPAG. Together, these findings indicate that adolescent alcohol exposure produces long-lasting alterations in pain sensitivity and ethanol responsiveness and suggest that altered recruitment of KOR-expressing vlPAG neurons may contribute to ethanol sensitivity in females.
First Page
87
Last Page
94
PubMed ID
42144041
Volume
134
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Albrechet-Souza, Lucas; Logarbo, Patrick J.; Min, Hla Y.; Ha, Linh; Wilson, Lisa L.; and Wills, Tiffany A., "Adolescent ethanol exposure produces sex-dependent modulation of ethanol-induced analgesia and cell type-specific vlPAG activation" (2026). School of Graduate Studies Faculty Publications. 586.
https://digitalscholar.lsuhsc.edu/sogs_facpubs/586
10.1016/j.alcohol.2026.05.002