UC Riverside

Exercise has a myriad of benefits for brain and body health. Wheel running is an animal model of physical activity, and artificial selection for increased levels of running in rodents can reveal how genes and the environment affect exercise physiology. I examined endocannabinoids (eCBs), neuroanatomy, and reward behavior in four replicate lines of mice bred for high voluntary wheel running (High Runners; HR), compared to four non-selected Control (C) lines. First, I examined the eCBs 2-arachidonoyl-sn-glycerol (2-AG) and anandamide (AEA) and eCB analogs docosahexaenoylglycerol (DHG), oleoylethanolamide (OEA), and docosahexaenoylethanolamide (DHEA) in the upper small-intestinal epithelium of male and female HR and C mice, housed with or without wheel access for six days. I found a significant 3-way interaction of linetype, wheel access, and sex for 2-AG and DHG. When compared to C mice, lines of HR mice had lower concentrations of 2-AG. Also, jejunal epithelial 2-AG was significantly correlated with circulating 2-AG (data from a prior study in the same mice). Second, I measured five key brain region volumes and cell densities of female HR and C mice, either given or not given wheel access for 10 weeks from weaning. The red nucleus and the hippocampus were significantly larger in HR compared to C brains, but no difference was observed for the basolateral amygdala, nucleus accumbens or ventral pallidum. The cell densities of each region were not statistically different between HR and C mice. Chronic wheel access did not affect the volume or cell density of any region. Third, I used a behavioral test of conditioned place preference (CPP) with methylphenidate and cocaine stimuli, as well as wheel access, in three separate studies to evaluate the extent to which genetic predisposition for exercise reward is associated with increased drug or exercise reward. Both HR and C mice displayed significant CPP for cocaine and methylphenidate, but with no statistical difference between linetypes for either drug. Neither HR nor C mice conditioned to wheel access. Altogether, I identified underlying traits that may contribute to the increased ability and/or motivation of HR mice for running ~3x more per day than C lines.