Alteration of empathy-related behaviors in two strains of mice expressing mutations of the α5 cholinergic nicotinic receptor subunit

Human genetic association studies have linked a single nucleotide polymorphism (SNP) of the alpha5 subunit of nicotinic acetylcholine receptors (nAChRs) to an increased risk of nicotine dependence, alcohol use disorders (AUDs) and schizophrenia. We used transgenic mice expressing either the SNP rs16969968 (termed 5SNP or 5KI) or a knockout of the Chrna5 gene (5KO) to investigate the role of 5-containing nAChRs (5*nAChRs) in emotion recognition and prosocial, rescuing-like behavioral tasks. We found that 5KO mice are impaired in the recognition of a negative affective state in a familiar peer, and displayed severely altered pro-social, altruistic behaviors, eventually assaulting peers in distress. In contrast, 5KI mice exhibited normal or improved emotion recognition and increased rescuing-like behavior. Importantly, effects of 5 mutations on emotion recognition were modulated by sex. These results demonstrate the critical implication of 5*nAChRs in emotion recognition and prosocial behaviors, revealing, sex-dependent patterns of these social emotional deficits in 5KI and 5KO mice. The current study also supports the view that 5KI and 5KO may provide a valuable preclinical model of Type I (female 5KI mice), and Type II (male 5KO mice) behavioral profiles of AUD.