IMR Press / JIN / Volume 20 / Issue 4 / DOI: 10.31083/j.jin2004094
Open Access Original Research
Repetitive binge-like consumption based on the Drinking-in-the-Dark model alters the microglial population in the mouse hippocampus
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1 Department of Biological & Biomedical Sciences, North Carolina Central University, Durham, NC 27707, USA
2 Department of Basic Pharmaceutical Sciences, Fred P. Wilson School of Pharmacy, High Point University, High Point, NC 27268, USA
*Correspondence: (S. Alex Marshall)
These authors contributed equally.
J. Integr. Neurosci. 2021, 20(4), 933–943;
Submitted: 28 September 2021 | Revised: 5 November 2021 | Accepted: 23 November 2021 | Published: 30 December 2021
Copyright: © 2021 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license (

Alcoholism causes various maladaptations in the central nervous system, including the neuroimmune system. Studies of alcohol-induced dysregulation of the neuroimmune system generally focus on alcohol dependence and brain damage, but our previous research indicates that repetitive binge-like consumption perturbs cytokines independent of cell death. This paper extends that research by examining the impact of binge-like consumption on microglia in the hippocampus and the amygdala. Microglia were assessed using immunohistochemistry following binge-like ethanol consumption based on Drinking-in-the-Dark model. Immunohistochemistry results showed that binge-like ethanol consumption caused an increase in Iba-1 immunoreactivity and the number of Iba-1+ cells after one Drinking-in-the-Dark cycle. However, after three Drinking-in-the-Dark cycles, the number of microglia decreased in the hippocampus. We showed that in the dentate gyrus, the average immunoreactivity/cell was increased following ethanol exposure despite the decrease in number after three cycles. Likewise, Ox-42, an indicator of microglia activation, was upregulated after ethanol consumption. No significant effects on microglia number or immunoreactivity (Iba-1 nor Ox-42) were observed in the amygdala. Finally, ethanol caused an increase in the expression of the microglial gene Aif-1 during intoxication and ten days into abstinence, suggesting persistence of ethanol-induced upregulation of microglial genes. Altogether, these findings indicate that repetitive binge-like ethanol is sufficient to elicit changes in microglial reactivity. This altered neuroimmune state may contribute to the development of alcohol use disorders.

Alcohol use disorder
Binge-like drinking
Fig. 1.
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