Alcohol Facilitates Social Dominance Via Activating Dopamine 1 Receptor-expressing Neurons in the Lateral Septum of Male Mice

Acute alcohol consumption reduces behavioral inhibition while increasing locomotor activity, aggression, and social dominance, which is related to the mesolimbic dopamine system. The lateral septum (LS) abundantly expresses Dopamine Receptor neurons that critically regulate social motivation, reinforcement, and reward processing, their specific role in mediating acute alcohol related behavior remains poorly understood. In the present study, the acute alcohol exposure model (AAE) of male mice was established with different alcohol concentrations, and a tube, social interaction and open field tests were performed to detect the social characteristics and activity status of mice. The activated state of dopamine 1 receptor (D1R)-expressing neurons and D2R neurons in each brain region was detected by immunofluorescence colocalization assay. Then D1R neurons in the lateral septum (LS) was specifically inhibited or activated in Drd1-Cre mice with designer receptors exclusively activated by designer drugs (DREADDs), and the behavioral changes were analyzed. The results indicated that mice exhibited enhanced social dominance and mobility after 50 min of gavage with 20% 1.3 g/kg alcohol, accompanied by the increased activity of D1R neurons in the LS. Inhibiting or activating LS D1R neurons decreased or enhanced acute alcohol-induced behavioral effects, respectively. These findings indicate that acute alcohol exposure activates the D1R neurons in the LS that can mediate increased social behavior and mobility in mice.

Acute alcohol; D1R neurons; Lateral septum; Social behavior.