Different brain oxidative and neuroinflammation status in rats during prolonged abstinence depending on their ethanol relapse-like drinking behavior: Effects of ethanol reintroduction

S Fernández-Rodríguez,M.J Cano-Cebrián,S Rius-Pérez,S Pérez,C Guerri,L Granero,T Zornoza,A Polache

doi:10.1016/j.drugalcdep.2022.109284

S Fernández-Rodríguez, M.J Cano-Cebrián + Show 6 more

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https://doi.org/10.1016/j.drugalcdep.2022.109284

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Abstract

RationaleAccumulating evidence suggests that chronic alcohol consumption is associated with excessive oxidative damage and neuroinflammatory processes and these events have been associated to early alcohol withdrawal. In the present research we wonder if brain oxidative stress and neuroinflammation remains altered during prolonged withdrawal situations and whether these alterations can be correlated with relapse behavior in alcohol consumption. The effects of alcohol reintroduction were also evaluated MethodsWe have used a model based on the alcohol deprivation effect (ADE) within a cohort of wild-type male Wistar rats. Two subpopulations were identified according to the alcohol relapse-like drinking behavior displayed (ADE and NO-ADE subpopulations). Oxidized and reduced glutathione content was determined within the hippocampus and the amygdala using a mass spectrometry method. The levels of mRNA of seven different inflammatory mediators in the prefrontal cortex of rats were quantified. All the analyses were performed in two different conditions: after 21-day alcohol deprivation (prolonged abstinence) and after 24 h of ethanol reintroduction in both subpopulations. ResultsADE and NO-ADE rats showed different endophenotypes. ADE rats always displayed a significant lower alcohol intake rate and ethanol preference than NO-ADE rats. The results also demonstrated the existence of altered brain redox and neuroinflammation status after prolonged abstinence exclusively in ADE rats. Moreover, when ethanol was reintroduced in the ADE subpopulation, altered oxidative stress and neuroinflammatory markers were restored. ConclusionsPresent findings provide new mechanisms underlying the neurobiology of relapse behavior and suggest the development of new pharmacological approaches to treat alcohol-induced relapse.

Highlights

Alcohol Use Disorders (AUDs), formerly called alcohol dependence or alcohol abuse, are complex, chronic disorders with a high relapse rate (Koob and Volkow, 2016; Rehm, 2011)
We have focused our present research on the hippocampus, amygdala and prefrontal cortex (PFC) as these brain areas are highly affected by ethanol consumption and abstinence-induced damage (Chefer et al, 2011; Elibol-Can et al, 2011; Roberto et al, 2004)
Data included in each framed-line rectangle, were used to perform a two-way analysis of variance (ANOVA) for repeated measures at each deprivation periods (DPs)

Summary

Introduction

Alcohol Use Disorders (AUDs), formerly called alcohol dependence or alcohol abuse, are complex, chronic disorders with a high relapse rate (Koob and Volkow, 2016; Rehm, 2011). Even after successful detoxification and abstinence treatment, an alcohol-dependent patient remains at risk of relapse. Drug craving may even incubate over time, leading to a relapse risk several months after detoxification (Pickens et al, 2011). Literature shows that 60–80% of abstinent alcoholics will relapse during their lifetime (Barrick and Connors, 2002; Weiss et al, 2001). Drug seeking and relapse are the main clinical problems related to AUDs. deepen the understanding of the underlying neurobiology of relapse behavior could be essential for improving available treatments to reduce the relapse rate or, to a lesser extent, reduce alcohol intake (Cannella et al, 2019; Reilly et al, 2014; Spanagel and Vengeliene, 2013)

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