title: Dopamine signaling in the dorsal striatum is essential for motivated behaviors: lessons from dopamine-deficient mice.
abstract: Genetically engineered mice that lack tyrosine hydroxylase in all dopaminergic neurons become hypoactive and aphagic, and they starve by 4 weeks of age. However, they can be rescued by daily treatment with l-dopa, which restores activity and feeding for about 10 hours. Thus, these mice can be examined in both dopamine-depleted and dopamine-replete states. A series of behavioral experiments lead to the primary conclusion that in the dopamine-depleted state these mice are not motivated to engage in goal-directed behaviors. Nevertheless, they still have a preference for sucrose, they can learn the location of food rewards, and they can form a conditioned-place preference for drugs. Dopamine signaling can be restored to the striatum by several different viral gene-therapy procedures. Restoring dopamine signaling selectively to the dorsal striatum is sufficient to allow feeding, locomotion, and reward-based learning. The rescued mice appear to have normal motivation to engage in all goal-directed behaviors that have been tested. The results suggest that dopamine facilitates the output from dorsal striatum, which provides a permissive signal allowing feeding and other goal-directed behaviors.
authors.affiliation: Howard Hughes Medical Institute and Department of Biochemistry, Box 357370, University of Washington, Seattle, WA 98195, USA. palmiter@u.washington.edu
authors.forename: Richard D
authors.initials: RD
authors.lastname: Palmiter
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D004298:Dopamine / Q000172:deficiency* / Q000378:metabolism*; D005247:Feeding Behavior; D051379:Mice; D009042:Motivation; D017072:Neostriatum / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D004298:Dopamine