Behavioral and Metabolome Differences between C57BL/6 and DBA/2 Mouse Strains: Implications for Their Use as Models for Depression- and Anxiety-Like Phenotypes

Mouse models are widely used to study behavioral phenotypes related to neuropsychiatric disorders. However, different mouse strains vary in their inherent behavioral and molecular characteristics, which needs to be taken into account depending on the nature of the study. Here, we performed a detailed behavioral and molecular comparison of C57BL/6 (B6) and DBA/2 (DBA) mice, two inbred strains commonly used in neuropsychiatric research. We analyzed anxiety-related and depression-like traits, quantified hippocampal and plasma metabolite profiles, and assessed total antioxidant capacity (ΤAC). B6 mice exhibit increased depression-like and decreased anxiety-related behavior compared to DBA mice. Metabolite level differences indicate alterations in amino acid, nucleotide and mitochondrial metabolism that are accompanied by a decreased TAC in B6 compared to DBA mice. Our data reveal multiple behavioral and molecular differences between B6 and DBA mouse strains, which should be considered in the experimental design for phenotype, pharmacological and mechanistic studies relevant for neuropsychiatric disorders.