title: Dysregulation of striatal dopamine signaling by amphetamine inhibits feeding by hungry mice.
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.
authors.affiliation: Department of Biochemistry and Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. caesia@u.washington.edu
authors.forename: Claire Matson
authors.initials: CM
authors.lastname: Cannon
authors.forename: Luna
authors.initials: L
authors.lastname: Abdallah
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Tecott
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: During
authors.forename: Richard D
authors.initials: RD
authors.lastname: Palmiter
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004299:Dopamine beta-Hydroxylase / Q000172:deficiency / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects*; D001068:Feeding and Eating Disorders / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D015316:Genetic Therapy / Q000379:methods; D006815:Hunger / Q000187:drug effects* / Q000502:physiology; D007980:Levodopa / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009478:Neuropeptide Y / Q000172:deficiency / Q000235:genetics; D044405:Receptor, Serotonin, 5-HT2C; D017447:Receptors, Dopamine D1 / Q000172:deficiency / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000172:deficiency / Q000235:genetics; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000172:deficiency / Q000235:genetics
chemical_list: D018765:Dopamine Uptake Inhibitors; D009478:Neuropeptide Y; D044405:Receptor, Serotonin, 5-HT2C; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D007980:Levodopa; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D004298:Dopamine