THE NEURAL BASIS OF HYPERACTIVE WHEEL RUNNING IN MICE

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The major goal of the proposed project is to investigate the neural basis of hyperactivity in a novel mouse model. Through artificial selection we have produced lines of mice that are internally motivated to run faster on running wheels than randombred controls, resulting in a 26-fold increase in wheel revolutions in a 24 hour period. Wheel-running in the hyperactive animals is composed of short bursts of activity separated by frequent short rests. High wheel-running mice are also more active in their home cages when deprived of wheels. The high-running mice may, therefore, be a good animal model for attention deficit hyperactivity disorder (ADHD). An association between deficiencies in dopamine transmission and ADHD has been suggested, and preliminary neuropharmacological results are consistent with the hypothesis that the hyperactive wheel running is caused by diminished dopaminergic function. To further explore the neural basis of genetic hyperactivity, I propose to examine whether: 1) apomorphine, and Ritalin(TM) attenuate wheel-running behavior in the high-running mice, 2) dopamine metabolism is slower in the high-running mice compared to controls at a given speed of running, and 3) the high-running mice contain fewer or smaller dopamine neurons in the ventral tegmental area. Together the proposed studies will help clarify the underlying neurochemistry and neuroanatomy of genetic hyperactivity.