Dopamine Signaling in the Dorsal Striatum Is Essential for Motivated Behaviors
Lessons from Dopamine-Deficient Mice
Richard D. Palmiter,
Richard D. Palmiter
Howard Hughes Medical Institute and Department of Biochemistry, University of Washington, Seattle, Washington, USA
Search for more papers by this authorRichard D. Palmiter,
Richard D. Palmiter
Howard Hughes Medical Institute and Department of Biochemistry, University of Washington, Seattle, Washington, USA
Search for more papers by this authorAddress for correspondence: Richard D. Palmiter, Howard Hughes Medical Institute and Department of Biochemistry, Box 357370, University of Washington, Seattle, WA 98195. [email protected]
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.
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