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Ann N Y Acad Sci. 2008;1129:35-46. doi: 10.1196/annals.1417.003.

Dopamine signaling in the dorsal striatum is essential for motivated behaviors: lessons from dopamine-deficient mice.

Author information

1
Howard Hughes Medical Institute and Department of Biochemistry, Box 357370, University of Washington, Seattle, WA 98195, USA. palmiter@u.washington.edu

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.

PMID:
18591467
PMCID:
PMC2720267
DOI:
10.1196/annals.1417.003
[Indexed for MEDLINE]
Free PMC Article

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