Dysregulation of striatal dopamine signaling by amphetamine inhibits feeding by hungry mice

Neuron. 2004 Oct 28;44(3):509-20. doi: 10.1016/j.neuron.2004.10.009.

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

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amphetamine / pharmacology*
  • Analysis of Variance
  • Animals
  • Behavior, Animal
  • Corpus Striatum / drug effects*
  • Dopamine / metabolism*
  • Dopamine Uptake Inhibitors / pharmacology*
  • Dopamine beta-Hydroxylase / deficiency
  • Dopamine beta-Hydroxylase / genetics
  • Dose-Response Relationship, Drug
  • Eating / drug effects
  • Feeding Behavior / drug effects*
  • Feeding and Eating Disorders / chemically induced
  • Feeding and Eating Disorders / genetics
  • Feeding and Eating Disorders / physiopathology
  • Feeding and Eating Disorders / therapy
  • Genetic Therapy / methods
  • Hunger / drug effects*
  • Hunger / physiology
  • Levodopa / pharmacology
  • Locomotion / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neuropeptide Y / deficiency
  • Neuropeptide Y / genetics
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Dopamine D1 / deficiency
  • Receptors, Dopamine D1 / genetics
  • Receptors, Dopamine D2 / deficiency
  • Receptors, Dopamine D2 / genetics
  • Time Factors
  • Tyrosine 3-Monooxygenase / deficiency
  • Tyrosine 3-Monooxygenase / genetics

Substances

  • Dopamine Uptake Inhibitors
  • Neuropeptide Y
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Levodopa
  • Amphetamine
  • Tyrosine 3-Monooxygenase
  • Dopamine beta-Hydroxylase
  • Dopamine