However, male rodent models have traditionally been used in genetic and pharmacological studies of depression. The prevalence and clinical characteristics of depression differ between women and men with women suffering from depression nearly twice as frequently as men during lifetime, independently of race or ethnicity ( Weissman and Klerman, 1977 Cyranowski et al., 2000 Andrade et al., 2003 Ford and Erlinger, 2004 Patten et al., 2006 Bromet et al., 2011 Salk et al., 2017).
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Additionally, tests that measure anxiety including open field, elevated plus maze and light/dark compartment are often performed complementary to depression tests for the full characterization of rodent models of neuropsychiatric disorders ( Belovicova et al., 2017). For example, the tail suspension and forced swim tests measure despair, the splash test measures apathy, while the sucrose preference test evaluates anhedonia ( Eltokhi et al., 2018 Becker et al., 2021). Several tests are usually performed to assess distinct components of depression in rodent models. These depression-like behaviors can be induced in rodents by several means including genetic, environmental, chemical and pharmacological manipulation and brain lesions. Still, different rodent models have shown high face validity to human depression and are used in preclinical studies. Because of the unique and complex features in addition to the subjective symptoms of human depression, the generation of valid and insightful depression models for the development of new therapeutic drugs is not straightforward. The symptoms include sadness, helplessness, guilt and loss of appetite, sexual desire, and interest in activities that once were pleasurable (for at least 2 weeks) along with recurrent thoughts of suicide ( McCarter, 2008 American-Psychiatric-Association, 2013). It affects approximately 4.4% of the world’s population with an incidence rate above the rate of global population growth ( Flux and Lowry, 2020). Our study gives insight into the behavioral experiments assessing depression and stresses the importance of considering strain, age and sex when evaluating neuropsychiatric-like traits in rodent models.ĭepression is a long-lasting heterogeneous neuropsychiatric disorder and one of the most common mental diseases, which places a significant economic burden on public health and decreases individuals’ quality of life ( Wittchen et al., 2011 Lim et al., 2012 Murray et al., 2013 Whiteford et al., 2013). Consistent with a previous study revealing sex differences in other anxiety tests in adolescent mice, male and females mice behaved differently in the hyponeophagia test at P27. Since anxiety-related behavioral tests are often performed together with depression tests in mouse models of neuropsychiatric disorders, we extended our study and included hyponeophagia as an anxiety test. Additionally, the 10-day interval during this sensitive period uncovered a strong impact on the behavioral outcome of C57BL/6N and FVB/N mice, highlighting a significant effect of maturation on behavioral patterns. Our experiments, performed at two different developmental stages during adolescence (P22–P26 and P32–P36), revealed strain but no sex differences in a set of depression-related tests, including tail suspension, sucrose preference and forced swim tests. Here, we investigated the baseline depression-like behaviors in male and female mice of three adolescent wild-type inbred strains, C57BL/6N, DBA/2, and FVB/N, that are typically used as background strains for mouse models of neuropsychiatric disorders. Still, the inclusion of female rodents in the behavioral analysis is mandatory to establish the origin of sex bias in depression. Although women are two times more likely to be diagnosed with depression compared to men, behavioral experiments on rodent models of depression are mainly performed in males based on the assumption that the estrous cycles in females may affect the behavioral outcome and cause an increase in the intrinsic variability compared to males. Modeling depression in rodents has been used to understand the pathophysiological mechanisms behind this disorder and create new therapeutics. Beyond the alarming public health problem, depression leads to morbidity across the entire age including adolescence and adulthood. Depression is a major neuropsychiatric disorder, decreasing the ability of hundreds of millions of individuals worldwide to function in social, academic, and employment settings.
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