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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31NS042872-01
Application #
6293606
Study Section
Special Emphasis Panel (ZRG1-IFCN-1 (01))
Program Officer
Spinella, Giovanna M
Project Start
2001-06-01
Project End
Budget Start
2001-06-01
Budget End
2002-05-31
Support Year
1
Fiscal Year
2001
Total Cost
$35,407
Indirect Cost
Name
University of Wisconsin Madison
Department
Zoology
Type
Schools of Arts and Sciences
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Li, Guo; Rhodes, Justin S; Girard, Isabelle et al. (2004) Opioid-mediated pain sensitivity in mice bred for high voluntary wheel running. Physiol Behav 83:515-24
Rhodes, Justin S; van Praag, Henriette; Jeffrey, Susan et al. (2003) Exercise increases hippocampal neurogenesis to high levels but does not improve spatial learning in mice bred for increased voluntary wheel running. Behav Neurosci 117:1006-16
Gammie, Stephen C; Hasen, Nina S; Rhodes, Justin S et al. (2003) Predatory aggression, but not maternal or intermale aggression, is associated with high voluntary wheel-running behavior in mice. Horm Behav 44:209-21
Rhodes, Justin S; Garland Jr, Theodore; Gammie, Stephen C (2003) Patterns of brain activity associated with variation in voluntary wheel-running behavior. Behav Neurosci 117:1243-56
Rhodes, J S; Garland, T (2003) Differential sensitivity to acute administration of Ritalin, apomorphine, SCH 23390, but not raclopride in mice selectively bred for hyperactive wheel-running behavior. Psychopharmacology (Berl) 167:242-50