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The Neurobiological Basis of Voluntary Exercise in Selectively-Bred High Runner Mice


Exercise is a rewarding behavior with a multitude of positive effects on the body and brain, and animals vary greatly in terms of how much they choose to exercise. I examined neurobiological changes that have occurred in four replicate lines of mice selectively bred for high voluntary wheel running as compared with four non-selected control lines.

First, I followed up on a study which showed that high runner (HR) mice have larger midbrains than control (C) mice. I wanted to determine which midbrain regions have increased in size, and whether 10 weeks of wheel access would affect their size and/or cell density. I found a significant interaction between linetype (HR vs. C) and wheel access in the periaqueductal grey (PAG) region, with wheel access increasing PAG volume in C mice, while decreasing it in HR mice. HR mice also tended to have a larger ventral tegmental area, a region involved in processing rewards.

Next, I examined plasma levels of two endocannabinoids, 2-arachidonylglycerol (2-AG) and anandamide (AEA), in male and female HR and C mice with or without 6 days of wheel access (as used in the routine selection protocol). I found a significant interaction between sex, linetype, and wheel access, with female mice having lower levels of 2-AG and wheel access lowering 2-AG in some subgroups. The amount of running in the 30 minutes before sampling was a significant predictor of AEA levels in mice with wheel access, and HR had lower levels than C.

My third chapter examined reward substitution. Mice were housed with or without wheels and given access to artificial sweeteners as competing rewards. Building on data previously collected, we showed that all mice drank more of the artificial sweetener blends compared to water, although this increase was significantly smaller in HR mice, and only when they had access to wheels. This result suggests that HR mice prefer the reward of wheel running over that from sweeteners.

Overall, I show that HR mice have evolved several neurobiological differences that contribute to their ability to voluntarily exercise ~3 times as much as C mice on a daily basis.

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