disorders 19 SUMMARY STATEMENT 20 Female fruit flies, like their human counterparts, are more prone to chronic stress-induced 21 mood disorders like anhedonia or reduced activity. This sexual dimorphism was more evident 22 in a biotic stress. 23ABSTRACT 24 Stress-induced mood disorders such as depression and anxiety are sexually dimorphic in 25 human beings. Studying behavioural stress-responses in non-human animal models can help 26 better understand the behavioural manifestations of these disorders and the dimorphism in 27 their prevalence. Here we explore how sexes show differential behavioural responses to 28 different chronic stressors, both abiotic and biotic, by using outbred populations of 29 Drosophila melanogaster. The behaviours studiednamely, anhedonia, motivation to 30 explore a novel habitat, locomotor activity and sleep levelshave been well-investigated in 31 human and rodent-based models of stress disorders. These behaviours were studied in the 32 context of two different stressorsmechanical perturbation and adult crowding. Responses to 33 stress were found to be sexually dimorphic, and stressed females showed more behavioural 34 changes, such as a reduced motivation to explore a novel habitat. Furthermore, adult 35 crowding caused a greater number of sexually dimorphic behavioural changes than 36 mechanical perturbation. For instance, while mechanical perturbation caused anhedonia 37 across sexes, only females were anhedonic after crowding. We thus make a case for 38 Drosophila melanogaster as a model system for studying sexual dimorphism in stress-39 induced mood disorders in humans. 40 41 42 43 Stress-induced mood disorders (SIMDs) such as depression (Krishnan and Nestler, 2008; Van 44 Praag, 2004) and anxiety (Shin and Liberzon, 2009) can cause debilitating psychological 45 symptoms including suicidal tendencies, loss of sleep or appetite and reduced interest in 46 pleasurable activities (World Health Organisation, 2017; see Cryan and Holmes, 2005; Wong 47 and Licinio, 2001 for reviews). Moreover, they have been etiologically associated with other 48 physiological ailments like type-2 diabetes (Knol et al., 2006), cardiac disease and 49 cerebrovascular disease (reviewed in Evans et al., 2005). In order to better manage and treat 50 these disorders, identifying therapeutic targets and drugs for SIMDs or enhancing the efficacy 51 of the current treatments (Wong and Licinio, 2004) has been a key focus for researchers for 52 over 60 years. Much of the research in this area has used animal models to investigate the 53 underlying symptoms and the predisposition to these disorders, as well as develop novel 54 therapeutic strategies. Mammals are often seen as natural models in which to study the stress-55 response, with rodent (see Abelaira et al., 2013; Cryan and Holmes, 2005; Willner, 2017; 56 Willner et al., 1992 for reviews), dog (Seligman and Maier, 1967) and primate (see Mendoza 57 et al., 2000 for a discussion) models being popular. Recently, it has been shown that 58 invertebrates,...
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