Sex differences in behavioral, cognitive and voluntary ethanol-intake effects in Dexamethasone-induced depression-like state in Wistar rat

The stress response is attached to psychosomatic and psychiatric disorders. Therefore, it is important to comprehend the underlying mechanisms influencing this relationship. Moreover, men and women respond differently to stress–both psychologically and biologically. These differences should be studied to have an enhanced understanding of the gender difference. However, researches shedding light on sex dimorphism implication have historically been insufficient. Based on observations that advocate the inclusion of sex as a biological variable in stress response, the present study was designed to explore sex differences in (i) depressive-like, (ii) anxiety-like behaviors, (iii) cognitive-like performances, and (iv) voluntary ethanol intake (VEI) in Wistar rat submitted to dexamethasone (DEX)-stress simulation. Rats were administered daily with DEX (1.5 mg/kg, s.c., 21 days) or vehicle. Behavior, cognitive, and VEI states of rats were evaluated in the following paradigms: forced swimming test (FST); saccharin preference test (SPT); open field test (OFT); elevated plus-maze test (EPMT); novelty suppressed feeding test (NSFT); spatial learning and memory in Morris water maze test (MWMT); VEI in two-bottle choice paradigm. DEX-treated rats showed a set of depression-like behaviors: increased time of immobility; reduced preference for saccharin consumption; increased anxiety-like behavior; cognitive impairments; and enhanced VEI. Sexual dimorphism was recorded in this study. Females were more impaired in FST, SPT, EPMT, NSFT, and VEI. Results demonstrate that DEX-treatment induced a behavioral alterations related to anxiety-depressive-like state with learning and memory impairments; confirm the facilitatory role of glucocorticoids on VEI and reveal sexual dimorphism in stress response.