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Behavioral, Neural, and Life History Correlates of Selective Breeding for High Voluntary Exercise in House Mice

Abstract

My research utilized a long-term artificial selection experiment in which mice (Mus domesticus) are selectively bred on the basis of voluntary exercise (high levels of voluntary wheel running: four replicate High Runner or HR lines) to address how a specific motivated behavior is generated in the brain, and how this may affect the performance of other motivated behaviors and organismic processes (e.g., reproduction).

I studied the endocannabinoid system, one signaling system involved in control of motivated behaviors via the perception of natural rewards. The endocannabinoid system is thought to play a role in voluntary wheel running in mice. In support of this, we found that HR mice, as compared to four non-selected Control lines, have a differential and sex-specific response to two drugs that affect the endocannabinoid system (Rimonabant (SR141716); WIN 55,212-2).

Secondly, I studied whether the HR and Control linesdiffer with respect to life history characteristics of dams and litters over a 10-generation span. I found that HR did not differ from Control in most measures of reproductive output or measures of maternal care.

Thirdly, I measured oxytocin receptor densities in several brain areas that reflect either neural dopaminergic connections or strong involvement in mouse social or parental behavior (or both). I did not find statistical differences between postpartum HR and Control dams.

Lastly, I allowed HR and Control mice wheel access for 6 days, after which, wheel access was blocked with screen mesh and a coffee-cup lid-barrier for one additional day. I found no statistical linetype difference in the proportion of mice that broke through the barrier. This indicates that HR and Control mice may be equally motivated to run on wheels; however, these results may have been influenced by confounding features of the experimental design.

In sum, these studies suggest that HR mice have sex-specifically diverged from Control mice in aspects of reward-related signaling; however, selection does not seem to influence the performance or regulation of reproduction in females, nor motivation break through a barrier for wheel-access in either sex.

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