Sex differences and similarities in depressive- and anxiety-like behaviour in the Wistar-Kyoto rat

Abstract

Depression is a debilitating psychiatric disorder that is highly comorbid with anxiety. Depression is twice as prevalent in women as in men, however, females remain underrepresented in preclinical research. The stress hyperresponsive Wistar-Kyoto (WKY) rat displays hypolocomotion in a novel aversive environment and depressive- and anxiety-like behaviours, which have been mostly characterised in males. The current study characterised behaviour in male and female rats in a battery of behavioural paradigms. Adult male and female WKY rats were tested in the open field and forced swim tests (tests with a locomotor component); and the marble burying, novelty-induced hypophagia and sucrose preference tests (tests with a minimal locomotor component) and 24 h home-cage locomotor activity was also monitored. The tests were compared against the Sprague-Dawley (SD) strain, a commonly used “control” strain. SD, but not WKY, females exhibited higher home-cage locomotor activity compared to males. In the open field, WKY rats of both sexes exhibited a significant reduction in locomotor activity and increased anxiety-like behaviour as demonstrated by reduced time in the aversive inner zone of the open field, compared to SD counterparts. In the marble burying test, WKY females, but not males, exhibited a trend towards increased burying, indicative of anxiety-like/neophobic behaviour. In comparison, WKY males, but not females, exhibited enhanced novelty-induced hypophagia, indicative of increased anxiety-like behaviour compared to SD rats. In the forced swim test, WKY rats of both sexes spent more time immobile compared with SD counterparts, indicating depressive-like behaviour. However, in comparison to SD rats, WKY males, but not females, exhibited anhedonic-like behaviour. In conclusion, WKY rats exhibit depressive- and anxiety-like behaviours that are complex and nuanced depending on the sex of the rat and testing conditions. This study supports the use of a varied test battery to fully characterise depression/anxiety-like behaviour in male and female rats.