RHODES, J.S.*; GAMMIE, S.C.; GARLAND, T., Jr.; Oregon Health & Science Univ., Portland, OR.; Univ. of Wisconsin-Madison, WI.; Univ. of California, Riverside, CA.: Neurobiology of mice selected for high voluntary wheel running

Selective breeding of house mice has been used to study the evolution of locomotor behavior. Our model consists of 4 replicate lines bred for increased voluntary running (S) and 4 bred randomly as controls (C). The major changes in S lines appear to have taken place in the brain rather than in capacities for exercise. The neurobiological profile is characteristic of genetic hyperactivity and/or high motivation for exercise as a natural reward (exercise addiction). Both genetic hyperactivity and motivation for natural rewards (such as food and sex), as well as drugs of abuse, have been associated with the function of the neuromodulator dopamine. In particular, drugs that block the dopamine transporter protein (such as Ritalin, cocaine, and GBR 12909) reduce the high-intensity running of S mice but have little effect on C mice. In preliminary studies of mice exercised on a treadmill, brain dopamine concentrations did not differ between S and C mice, but other pharmacological studies using agonists and antagonists indicate that the function of dopamine receptors is reduced in S mice. Brain imaging by Fos immunohistochemistry identified several key regions that appear to play a role in the differential response to Ritalin and increased motivation for running in S mice. Other brain regions were identified as playing a role in controlling the intensity of wheel running. Interestingly, wheel running increases the formation of new neurons in the hippocampus, a region important for learning and memory. We discuss biomedical implications and point out some advantages of an evolutionary perspective in neurobiology. Supported by NSF IBN-0212567 to T.G.