P.0712 Exercise mitigates the negative effects of a cafeteria diet on antidepressant-like behaviour in adult male rats

Abstract

Depression, which is often comorbid with anxiety, is a common neuropsychiatric disorder that significantly impacts quality of life [1]. It is associated with disruptions in hippocampal neurogenesis [2]. Poor diet has been reported to increase risk of depression and anxiety, although previous research on the impact of diet has mainly focussed on early periods of life [3]. On the other hand, studies have shown that exercise can ameliorate symptoms of depression [4]. Not much is yet known about the interaction between cafeteria diet, which is high in fat/sugar and mimics human fast food diets, and exercise during adulthood on hippocampal neurogenesis and behaviour. Thus, this study aimed to determine whether exercise can mitigate any negative effects of a cafeteria diet during adulthood on depressive- and anxiety-like behaviour and hippocampal neurogenesis. Male Sprague-Dawley rats were fed standard chow with or without additional cafeteria foods (e.g. crisps, cookies), and were housed under sedentary conditions or allowed voluntary running exercise. At the start of intervention, animals were injected with 150mg/kg BrdU i.p. to label newly born hippocampal neurons. After four weeks, anhedonia, antidepressant-like and anxiety-like behaviours were assessed using the Elevated Plus Maze, Female Urine Sniffing, Novelty-suppressed Feeding, Open Field, and Forced Swim tests. Animals were allowed continued access to cafeteria diet and/or running wheels during the testing period. Results were tested for outliers with Grubbs' and for normality using the Shapiro-Wilk test. Data were analysed for statistical differences using two-way ANOVA followed by Tukey's HSD for post-hoc analyses, or using Kruskal-Wallis followed by pairwise Wilcoxon rank-sum tests, as appropriate. Hippocampal neurogenesis was analysed by measuring survival of newly born hippocampal neurons using immunohistochemical staining of BrdU and NeuN, a marker of mature neurons. In sedentary rats, immobility in the forced swim test, a measure of antidepressant-like behaviour, was increased by cafeteria diet compared to standard chow (p<0.05), and this effect was prevented by exercise (p<0.05). Anhedonia, measured in the female urine sniffing test, was not affected by any intervention. In behavioural tests of anxiety, there was a trend (all p=0.06) for exercise to exert anxiolytic effects. Specifically, in the novelty-suppressed feeding test exercise tended to decrease latency to eat in both control (p=0.06) and cafeteria diet (p=0.06) groups compared to their respective sedentary groups, and exercise tended to increase time spent in open arms in the elevated plus maze (p=0.06). Behavioural effects were not due to alterations in general locomotor activity, and control and cafeteria diet groups did not differ in running distance. Potential impacts on hippocampal neurogenesis are currently being investigated. This study demonstrates a negative effect of a cafeteria diet on antidepressant-like behaviour in adult male rats, and shows for the first time that this can be mitigated by voluntary running exercise. While no anxiogenic effect of the cafeteria diet was observed, exercise induced an anxiolytic-like effect although this did not quite reach statistical significance. These data contribute to the understanding of lifestyle influences on depression and anxiety, and yield novel insights for preventative strategies for neuropsychiatric disorders. Conflict of interest Disclosure statement: Minke Nota is a recipient of an Irish Research Council PhD Scholarship (GOIPG/2019/4514). This work was also funded by Science Foundation Ireland under Grant Number SFI/IA/1537.Copyright © 2021