Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Adenoviridae / genetics
-
Animals
-
Dietary Sucrose / pharmacology
-
Dopamine / analysis
-
Dopamine / biosynthesis
-
Dopamine / genetics*
-
Dopamine Agents / pharmacology
-
Feeding Behavior / drug effects
-
Feeding Behavior / physiology
-
Female
-
Food Preferences / drug effects
-
Food Preferences / physiology
-
Immunohistochemistry
-
Levodopa / pharmacology
-
Male
-
Mice
-
Mice, Inbred C57BL
-
Mice, Mutant Strains*
-
Movement / drug effects
-
Movement / physiology
-
Neostriatum / metabolism*
-
Nesting Behavior / drug effects
-
Nesting Behavior / physiology
-
Nucleus Accumbens / metabolism
-
Recombinant Proteins / genetics
-
Transduction, Genetic
-
Tyrosine 3-Monooxygenase / analysis
-
Tyrosine 3-Monooxygenase / genetics*
-
Tyrosine 3-Monooxygenase / metabolism
Substances
-
Dietary Sucrose
-
Dopamine Agents
-
Recombinant Proteins
-
Levodopa
-
Tyrosine 3-Monooxygenase
-
Dopamine