Development of a Mouse Model to Study Alcohol Withdrawal-Induced Allodynia [ASPET 2023 Annual Meeting Abstract - Central Nervous System Pharmacology - Neuropharmacology]

Abstract ID 16458

Poster Board 571

Alcohol use disorder is a prevalent psychiatric disorder affecting nearly 15 million people in the United States. Individuals who wish to cease to consume alcohol are often met with the effects of the dark side of addiction after alcohol withdrawal. One detrimental withdrawal symptom is increased pain sensitivity, which may contribute to relapse to attain the analgesic effect of alcohol. The present study investigated alcohol withdrawal-induced allodynia in a mouse model of chronic ethanol administration and assessed the effectiveness of a histone deacetylase inhibitor in preventing the development of allodynia. Male and female C57BL/6J mice were first given Lieber-DeCarli control liquid diet for 5 days. The mice were then separated into control and ethanol (5% vol/vol) diet groups and fed their respective diets for 10 days. On day 11, the ethanol and control diet-fed mice were given an oral gavage of either ethanol (5 g kg-1 body weight) or an isocaloric maltose/dextran solution, respectively. Ethanol diet-fed mice then underwent ethanol withdrawal for 24 hours. We found that mice given ethanol diet plus withdrawal exhibited allodynia compared to control mice. The allodynic response persisted for at least 48 hours and then slowly returned to baseline levels. Finally, we performed an experiment in which we treated mice during ethanol withdrawal with suberoyl anilide hydroxamic acid (SAHA), a pan-histone deacetylase (HDAC) inhibitor and found that SAHA attenuated the allodynic response in ethanol diet-fed plus withdrawal mice. These results demonstrate that chronic ethanol diet plus withdrawal induces allodynia, and SAHA prevents the development of this pain. This model can be used to further understand the molecular mechanisms and the effectiveness of pharmacological interventions in ethanol withdrawal-induced pain sensitivity.

Supported by NIAAA U01 AA020912 and P50 AA022538 (AWL).

Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics

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