Effects of chronic emotional stress on the behavior of mice with Q31l and L100P mutations in the DISC1 gene

Both genetic and environmental factors, which causing stress, are involved in the etiology of mental illness. Mutations in the DISC1 gene are in themselves predictors of the psychopathologies’ development, at the same time, there are no data about chronic stress effects on the emotionally conditioned (affective) behavior of an organism with mutations in this gene. Objective: to study the behavioral response features of mice with point mutations in the DISC1 gene after an unpredictable emotional stressful impact with different duration. Materials and Methods. Testing was carried out on 3-4-month-old male mice of three genetic strains: C56BL/6, DISC1-Q31L-/- (Q31L) and DISC1-L100P-/-). To study the behavioral response mice with mutations Q31L and L100P, characterized by depression-like and schizophrenia-like behavior, were subjected to 2 and 4 weeks chronic unpredictable mild stress (CUMS). After that, their anxiety, motor and exploratory activity, emotionality, depressive-like and obsessive-compulsive behavior, social motivation, and preference were assessed. It was found that two-week stress increased anxiety and depression-like behavior in Q31L mice, and four-week stress increased their motor activity, but had no effect on anxiety and depression-like status. In L100P mice, both two- and four-weeks stress resulted in depression-like behavior. In addition, two-week stress increased emotionality and social interaction, while four-week stress decreased mice exploratory activity. Thus, the genetically determined depression-like state in Q31L mice increases after two weeks stress exposure, while L100P mice with a genetically determined schizophrenialike phenotype form a depression-like status after chronic stress of different duration.