Volume 1129, Issue 1 p. 35-46

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

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First published: 28 June 2008
Citations: 277
Address 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.