PT  - JOURNAL ARTICLE
AU  - Harold L. Haun
AU  - Shannon L. D’Ambrosio
AU  - Thomas L. Kash
TI  - Activation of the dorsal septum increases alcohol consumption in male C57BL/6J mice
AID  - 10.1101/2022.01.15.476378
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.01.15.476378
4099  - http://biorxiv.org/content/early/2022/01/17/2022.01.15.476378.short
4100  - http://biorxiv.org/content/early/2022/01/17/2022.01.15.476378.full
AB  - Binge drinking is a common pattern of excessive alcohol consumption associated with Alcohol Use Disorder (AUD) and unraveling the neurocircuitry that promotes this type of drinking is critical to the development of novel therapeutic interventions. The septal region was once a focal point of alcohol research yet has seen limited study over the last decade in relation to binge drinking. Numerous studies point to involvement of the dorsal septum (dSep) in excessive drinking and withdrawal, but few studies have manipulated this region in the context of binge drinking behavior. The present experiments were primarily designed to determine the effect of chemogenetic manipulation of the dSep on binge-like alcohol drinking in male and female C57BL/6J mice. Mice received bilateral infusion of AAVs harboring hM4Di, hM3Dq, or mCherry into the dSep and subjects were challenged with systemic administration of clozapine-N-oxide (CNO; 3 mg/kg) and vehicle (saline; 0.9%) in the context of binge-like alcohol consumption, locomotor activity, and sucrose drinking. CNO-mediated activation (hM3Dq) of the dSep resulted in a significant increase in binge-like alcohol consumption, locomotor activity, and sucrose intake in male mice. DSep activation promoted sucrose drinking in female mice, but alcohol intake and locomotor activity were unaffected. Conversely, silencing (hM4Di) of the dSep modestly decreased locomotor activity in males and did not influence alcohol or sucrose intake in either sex. Lastly, CNO was without effect in mCherry-expressing control groups. These data support a role for the dSep in promoting excessive, binge-like drinking behavior in a sex-dependent fashion and suggests a broad role for the region in the modulation of locomotor activity as well as general appetitive behavior such as sucrose drinking.Competing Interest StatementThe authors have declared no competing interest.