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

Abstract

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 (ΤΑC). 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 TACin 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.

Do greater levels of in-cage waking inactivity in laboratory mice reflect a spontaneous depression-like symptom? A pharmacological investigation

“…C57BL/6Js are more prone to display depression-like profiles e.g. [25,42,43], although phenotypes may vary between laboratories e.g. [44], and greater IBA was observed in DBA/2Js in [45].…”

Multi-Omics Analysis Reveals Myelin, Presynaptic and Nicotinate Alterations in the Hippocampus of G72/G30 Transgenic Mice

“…Metabolomics is a powerful approach to detect altered biosignatures in psychopathologies [39], which we have implemented to disentangle molecular profiles of neuropsychiatric phenotypes [40][41][42][43] as well as responses to pertinent therapeutic interventions [44][45][46][47][48][49][50]. Here, we used a targeted metabolomics platform to compare G72Tg and WT mice and identified lower nicotinate levels in G72Tg hippocampi.…”

Deciphering the Metabolome under Stress: Insights from Rodent Models

“…Basal behavior among different mouse strains differs. In a comparative analysis of C57BL/6 and DBA/2 mice, we found that C57BL/6 mice are characterized by elevated depression-like and reduced anxiety-like behavior compared to DBA/2 mice [ 127 ]. Accordingly, the hippocampal and plasma metabolic metabolomic profiles were different between the two mouse strains.…”