Adolescent ethanol drinking promotes hyperalgesia, neuroinflammation and serotonergic deficits in mice that persist into adulthood

Kanza M Khan; Gabrielle Bierlein-De La Rosa; Natalie Biggerstaff; Selvakumar Govindhasamy Pushpavathi; Ruixiang Wang; Suzanne Mason; Michael E Dailey; Catherine A Marcinkiewcz

doi:10.1016/j.bbi.2022.07.160

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Adolescent ethanol drinking promotes hyperalgesia, neuroinflammation and serotonergic deficits in mice that persist into adulthood

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Adolescent ethanol drinking promotes hyperalgesia, neuroinflammation and serotonergic deficits in mice that persist into adulthood

Kanza M Khan, Gabrielle Bierlein-De La Rosa, Natalie Biggerstaff, Selvakumar Govindhasamy Pushpavathi, Ruixiang Wang, Suzanne Mason, Michael E Dailey and Catherine A Marcinkiewcz

Brain, behavior, and immunity, Vol.107, pp.419-431

01/2023

DOI: 10.1016/j.bbi.2022.07.160

PMCID: PMC10289137

PMID: 35907582

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https://pmc.ncbi.nlm.nih.gov/articles/PMC10289137/pdf/nihms-1908924.pdfView

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Abstract

Adolescent alcohol use can permanently alter brain function and lead to poor health outcomes in adulthood. Emerging evidence suggests that alcohol use can predispose individuals to pain disorders or exacerbate existing pain conditions, but the underlying neural mechanisms are currently unknown. Here we report that mice exposed to adolescent intermittent access to ethanol (AIE) exhibit increased pain sensitivity and depressive-like behaviors that persist for several weeks after alcohol cessation and are accompanied by elevated CD68 expression in microglia and reduced numbers of serotonin (5-HT)-expressing neurons in the dorsal raphe nucleus (DRN). 5-HT expression was also reduced in the thalamus, anterior cingulate cortex (ACC) and amygdala as well as the lumbar dorsal horn of the spinal cord. We further demonstrate that chronic minocycline administration after AIE alleviated hyperalgesia and social deficits, while chemogenetic activation of microglia in the DRN of ethanol-naïve mice reproduced the effects of AIE on pain and social behavior. Chemogenetic activation of microglia also reduced tryptophan hydroxylase 2 (Tph2) expression and was negatively correlated with the number of 5-HT-immunoreactive cells in the DRN. Taken together, these results indicate that microglial activation in the DRN may be a primary driver of pain, negative affect, and 5-HT depletion after AIE.

Details

Title: Subtitle: Adolescent ethanol drinking promotes hyperalgesia, neuroinflammation and serotonergic deficits in mice that persist into adulthood
Creators: Kanza M Khan - University of Iowa
Gabrielle Bierlein-De La Rosa
Natalie Biggerstaff
Selvakumar Govindhasamy Pushpavathi
Ruixiang Wang
Suzanne Mason
Michael E Dailey
Catherine A Marcinkiewcz
Resource Type: Journal article
Publication Details: Brain, behavior, and immunity, Vol.107, pp.419-431
DOI: 10.1016/j.bbi.2022.07.160
PMID: 35907582
PMCID: PMC10289137
NLM abbreviation: Brain Behav Immun
ISSN: 0889-1591
eISSN: 1090-2139
Grant note: DOI: 10.13039/100000027, name: National Institute on Alcohol Abuse and Alcoholism, award: R00 AA024215, R01 AA028931; DOI: 10.13039/100000065, name: National Institute of Neurological Disorders and Stroke; DOI: 10.13039/100000874, name: Brain and Behavior Research Foundation, award: 27530; DOI: 10.13039/100000002, name: National Institutes of Health
Language: English
Electronic publication date: 07/27/2022
Date published: 01/2023
Academic Unit: Iowa Neuroscience Institute; Biology; Neuroscience and Pharmacology
Record Identifier: 9984296206902771

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