Genetically selected alcohol-preferring msP rats to study alcohol use disorder: Anything lost in translation?

NEUROPHARMACOLOGY

卷:186

Review

Borruto, Anna Maria¹  Stopponi, Serena¹  Li, Hongwu²  Weiss, Friedbert³  Roberto, Marisa⁴  Ciccocioppo, Roberto¹ 

[1] Univ Camerino, Pharmacol Unit, Sch Pharm, Via Madonna Carceri 9, I-62032 Camerino, MC, Italy

[2] Changchun Univ Technol, Coll Chem Engn, Changchun, Peoples R China

[3] Scripps Res Inst, Dept Neurosci, La Jolla, CA 92037 USA

[4] Scripps Res Inst, Dept Mol Med, La Jolla, CA 92037 USA

关键词: Alcoholism;    Sex differences;    Genetic selection;    Animal models;    Relapse;    Self-administration;    fMRI;    Brain imaging;   

DOI  :  10.1016/j.neuropharm.2020.108446

来源: Elsevier

【 摘 要 】

For several decades, genetically selected alcohol-preferring rats have been successfully used to mimic and study alcohol use disorders (AUD). These rat lines have been instrumental in advancing our understanding of the neurobiology of alcoholism and enabling pharmacological studies to evaluate drug efficacy on alcohol drinking and relapse. Moreover, the results of these studies have identified genetic variables that are linked to AUD vulnerability. This is an up-to-date review that focuses on genetically selected Marchigian Sardinian alcohol preferring (msP) rats. To support the translational relevance of the findings that are obtained from msP rats and highlight important similarities to AUD patients, we also discuss the results of recent brain imaging studies. Finally, to demonstrate the importance of studying sex differences in animal models of AUD, we present original data that highlight behavioral differences in the response to alcohol in male and female rats. Female msP rats exhibited higher alcohol consumption compared with males. Furthermore, msP rats of both sexes exhibit higher anxiety-and depressive-like behaviors in the elevated plus maze and forced swim test, respectively, compared with unselected Wistar controls. Notably, voluntary alcohol drinking decreases foot-shock stress and depressive like behavior in both sexes, whereas anxiety-like behavior in the elevated plus maze is attenuated only in males. These findings suggest that male and female msP rats both drink high amounts of alcohol to self-medicate negative affective symptoms. For females, this behavior may be driven by an attempt to treat stress and depressive-like conditions. For males, generalized anxiety appears to be an important additional factor in the motivation to drink alcohol.

【 授权许可】

Free