Dopamine production in the caudate putamen restores feeding in dopamine-deficient mice.
Dopamine-deficient (DD) mice cannot synthesize dopamine (DA) in dopaminergic neurons due to selective inactivation of the tyrosine hydroxylase gene in those neurons. These mice become hypoactive and hypophagic and die of starvation by 4 weeks of age. We used gene therapy to ascertain where DA replacement in the brain restores feeding and other behaviors in DD mice. Restoration of DA production within the caudate putamen restores feeding on regular chow and nest-building behavior, whereas restoration of DA production in the nucleus accumbens restores exploratory behavior. Replacement of DA to either region restores preference for sucrose or a palatable diet without fully rescuing coordination or initiation of movement. These data suggest that a fundamental difference exists between feeding for sustenance and the ability to prefer rewarding substances.
Szczypka
M S
MS
Howard Hughes Medical Institute and, Department of Biochemistry, Box 357370, University of Washington, Seattle, WA 98195, USA.
Kwok
K
K
Brot
M D
MD
Marck
B T
BT
Matsumoto
A M
AM
Donahue
B A
BA
Palmiter
R D
RD
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D019422:Dietary Sucrose / Q000494:pharmacology; D004298:Dopamine / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D015259:Dopamine Agents / Q000494:pharmacology; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D005518:Food Preferences / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009068:Movement / Q000187:drug effects / Q000502:physiology; D017072:Neostriatum / Q000378:metabolism*; D009425:Nesting Behavior / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics; D014161:Transduction, Genetic; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000235:genetics* / Q000378:metabolism
D019422:Dietary Sucrose; D015259:Dopamine Agents; D011994:Recombinant Proteins; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine