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Effect of calorie restriction on motivation to exercise and the steroid profile of female rats Liu, Megan

Abstract

Exercise is beneficial for the body, including the brain. Despite extensive research on the benefits of exercise, the neural and endocrine mechanisms controlling the motivation to exercise remain largely unknown. Wheel running is inherently rewarding for rodents and can be used to model voluntary exercise. Steroid hormones such as corticosterone, testosterone, and 17β-estradiol influence wheel running. Previous rodent studies have assessed wheel running performance, but this measure fails to distinguish between physical ability and motivation. The primary objective of this study was to validate a novel operant task for specifically measuring the motivation to run in rats. Females run more than males, and calorie restriction increases wheel running in rats. Here, adult female rats were calorie restricted (CR) or fed ad libitum (AL), and their motivation to exercise was assessed using a novel progressive ratio task in which lever pressing was paired with the opportunity to wheel run for 1 min. CR rats ran significantly more and reached a significantly higher breakpoint (i.e., last ratio not completed) than AL rats, indicating that calorie restriction increased both running performance and the motivation to run. A secondary objective was to explore whether steroids in the brain modulate the motivation to exercise. A panel of steroids including corticosterone, testosterone, and 17β-estradiol were measured in blood and microdissected brain regions after the end of the behavioural experiment using liquid chromatography tandem mass spectrometry (LC-MS/MS). Levels of testosterone and the less potent androgen androstenedione in the brain were altered by calorie restriction in a region-specific manner. Given that androgens have previously been shown to increase wheel running and calorie restriction increased the motivation to run in the current study, these results suggest that the motivation to exercise may be modulated by androgen signaling in the brain. To our knowledge, this study is the first to directly investigate the neuroendocrine mechanisms of the motivation to exercise. This work establishes a simple, specific, and effective operant task for assessing the motivation to exercise in rats and provides insight into potential neurosteroidal mechanisms modulating this behaviour.

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Attribution-NonCommercial-NoDerivatives 4.0 International