Dysregulation of striatal dopamine signaling by amphetamine inhibits feeding by hungry mice.
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.
Cannon
Claire Matson
CM
Department of Biochemistry and Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. caesia@u.washington.edu
Abdallah
Luna
L
Tecott
Laurence H
LH
During
Matthew J
MJ
Palmiter
Richard D
RD
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
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