Sex difference in depression: Which animal models mimic it.

Depression affects both women and men, but women are 2 times more susceptible to the incidence of depression. Although a number of studies report sex differences in stress responses, it remains unclear which animal models of depression can better mimic the sex difference in human depression. The majority of stress models used male rodents whereas fewer studies included females. The aims of this study were to determine which rat stress models mimic the sex difference in depression and to identify sex-specific risk factors for depression model-induced depression-like behaviors. Here, we compared subchronic variable stress (SCVS) and chronic unpredictable mild stress (CUMS) models to evaluate the susceptibility versus resilient phenotypes in male and female rats. SCVS induced depression-like behaviors in female rats only. The CUMS paradigm was more likely to induce depression-like behaviors in male rats. Furthermore, to explore the underlying mechanisms, we used quantitative reverse transcriptase polymerase chain reaction to examine and compare the messenger RNA (mRNA) levels of various transcripts previously shown to be involved in psychiatric disorders in RNA-sequencing/microarray studies including serotonin receptor-7, early growth response-2, histone deacetylase-2, roundabout guidance receptor-2 (Robo2), serum/glucocorticoid regulated kinase-2, orthodenticle homeobox-2, parathyroid hormone-2 receptor, and neuronal PAS domain protein-4 in the hippocampus after exposure of rats to SCVS and CUMS. Our results showed that SCVS significantly altered the mRNA levels of neuronal PAS domain protein-4, orthodenticle homeobox-2, Robo2, parathyroid hormone-2 receptor, and serum/glucocorticoid regulated kinase-2 in the female hippocampus only, and histone deacetylase-2 in only the male hippocampus. CUMS significantly changed the mRNA levels of one transcript (Robo2) in the female hippocampus only when compared with SCVS. Overall, this study shows that SCVS can be used to study sex differences in depression-like behaviors in rats. (PsycInfo Database Record (c) 2020 APA, all rights reserved).