Journal article
Impact of Adolescent Ethanol Binge on Serotonin Signaling and Pain Sensitivity Post-Withdrawal
Alcohol (Fayetteville, N.Y.), Vol.129, pp.58-68
12/2025
DOI: 10.1016/j.alcohol.2025.09.001
PMCID: PMC12949556
PMID: 40939668
Abstract
Adolescence is a critical neurodevelopmental period characterized by heightened neuroplasticity. While the acute effects of binge ethanol (EtOH) consumption are documented, its long-term impact on both pain sensitivity and microglial activation during adolescence remains unclear. Given serotonin's (5-HT) known involvement in pain processing and sensitivity to EtOH, this study examined the effects of adolescent EtOH binge on microglia-induced neuroinflammation in serotonergic nuclei, downstream 5-HT signaling, and pain sensitivity at different time points after EtOH withdrawal. Adolescent male C57BL/6J mice received triweekly oral gavage of 20% EtOH or water for 4 weeks and were assessed after 24 hours and 3 weeks post-withdrawal. We used immunohistochemistry to assess neuroinflammation in the dorsal raphe, median raphe, and raphe magnus by labeling 5-HT, CD68, and P2Y12. Further analyses examined downstream signaling via 5-HT and serotonin transporter (SERT) expression in the nucleus accumbens, anterior cingulate cortex, thalamus, amygdala, hypothalamus, and raphe magnus. Pain sensitivity was then assessed using the Hargreaves test. EtOH exposure led to widespread serotonergic and neuroinflammatory changes. Significant increases in microglia-induced neuroinflammation were observed in the dorsal raphe nucleus, median raphe nucleus, and raphe magnus nucleus after both 24 hours and 3 weeks post-withdrawal, along with significant deficits in 5-HT. Similar 5-HT deficits were observed in downstream regions-notably in the anterior cingulate cortex, thalamus, amygdala, and hypothalamus-at varying time points post-withdrawal. EtOH-exposed mice also showed lasting hyperalgesia at both 24 hours and 3 weeks post-withdrawal that persisted for up to 9 weeks. These results suggest that persistent hyperalgesia following adolescent EtOH binge may be driven by changes in serotonergic function and microglial activation.
Details
- Title: Subtitle
- Impact of Adolescent Ethanol Binge on Serotonin Signaling and Pain Sensitivity Post-Withdrawal
- Creators
- Alexander James Feller - University of IowaLouis John Kolling - University of IowaTien Tran - Department of Neuroscience and Pharmacology, University of Iowa, Iowa City, Iowa, USAShafa Ismail - University of IowaJessica Marie Hunter Alberhasky - University of IowaSamuel Cole Luciano - University of IowaCatherine Anne Marcinkiewcz - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Alcohol (Fayetteville, N.Y.), Vol.129, pp.58-68
- DOI
- 10.1016/j.alcohol.2025.09.001
- PMID
- 40939668
- PMCID
- PMC12949556
- NLM abbreviation
- Alcohol
- ISSN
- 1873-6823
- eISSN
- 1873-6823
- Publisher
- ELSEVIER SCIENCE INC
- Grant note
- United States (US) Department of Veteran Affairs Merit Award: I01 BX005778 National Institute on Alcohol Abuse and Alcoholism (NIAAA): R01 AA028931 National Institute on Aging (NIA): F32 AG081496 Summer Research Fellowship
This work was supported by the United States (US) Department of Veteran Affairs Merit Award I01 BX005778 and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) R01 AA028931. LK was supported by funding from the National Institute on Aging (NIA) F32 AG081496. AF was supported by a Summer Research Fellowship. We thank Yu Xu for performing animal husbandry.
- Language
- English
- Electronic publication date
- 09/10/2025
- Date published
- 12/2025
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984962644502771
Metrics
9 Record Views