Abstract
Amphetamine (AMPH) releases monoamines, transiently stimulates locomotion, and inhibits feeding. Using a genetic approach, we show that mice lacking dopamine (DA-deficient, or DD, mice) are resistant to the hypophagic effects of a moderate dose of AMPH (2 microg/g) but manifest normal AMPH-induced hypophagia after restoration of DA signaling in the caudate putamen by viral gene therapy. By contrast, AMPH-induced hypophagia in response to the same dose of AMPH is not blunted in mice lacking the ability to make norepinephrine and epinephrine (Dbh(-/-)), dopamine D(2) receptors (D2r(-/-)), dopamine D(1) receptors (D1r(-/-)), serotonin 2C receptors (Htr2c(-/Y)), neuropeptide Y (Npy(-/-)), and in mice with compromised melanocortin signaling (A(y)). We suggest that, at this moderate dose of AMPH, dysregulation of striatal DA is the primary cause of AMPH-induced hypophagia and that regulated striatal dopaminergic signaling may be necessary for normal feeding behaviors.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amphetamine / pharmacology*
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Analysis of Variance
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Animals
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Behavior, Animal
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Corpus Striatum / drug effects*
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Dopamine / metabolism*
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Dopamine Uptake Inhibitors / pharmacology*
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Dopamine beta-Hydroxylase / deficiency
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Dopamine beta-Hydroxylase / genetics
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Dose-Response Relationship, Drug
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Eating / drug effects
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Feeding Behavior / drug effects*
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Feeding and Eating Disorders / chemically induced
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Feeding and Eating Disorders / genetics
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Feeding and Eating Disorders / physiopathology
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Feeding and Eating Disorders / therapy
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Genetic Therapy / methods
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Hunger / drug effects*
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Hunger / physiology
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Levodopa / pharmacology
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Locomotion / drug effects
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Neuropeptide Y / deficiency
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Neuropeptide Y / genetics
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Receptor, Serotonin, 5-HT2C
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Receptors, Dopamine D1 / deficiency
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Receptors, Dopamine D1 / genetics
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Receptors, Dopamine D2 / deficiency
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Receptors, Dopamine D2 / genetics
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Time Factors
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Tyrosine 3-Monooxygenase / deficiency
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Tyrosine 3-Monooxygenase / genetics
Substances
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Dopamine Uptake Inhibitors
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Neuropeptide Y
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Receptor, Serotonin, 5-HT2C
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Receptors, Dopamine D1
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Receptors, Dopamine D2
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Levodopa
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Amphetamine
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Tyrosine 3-Monooxygenase
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Dopamine beta-Hydroxylase
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Dopamine