Dysregulation of dopamine signaling in the dorsal striatum inhibits feeding.
Dopamine signaling is an important component of many goal-directed behaviors, such as feeding. Acute disruption of dopamine signaling using pharmacological agents tends to inhibit normal feeding behaviors in rodents. Likewise, genetically engineered dopamine-deficient (DD) mice are unable to initiate sufficient feeding and will starve by approximately 3 weeks of age if untreated. Adequate feeding by DD mice can be achieved by daily administration of L-3,4-dihydroxyphenylalanine (L-dopa), a precursor of dopamine, which can be taken up by dopaminergic neurons, converted to dopamine, and released in a regulated manner. In contrast, adequate feeding cannot be restored with apomorphine (APO), a mixed agonist that activates D1 and D2 receptors. Viral restoration of dopamine production in neurons that project to the dorsal striatum also restores feeding in DD mice. Administration of amphetamine (AMPH) or nomifensine (NOM), drugs which increase synaptic dopamine concentration, inhibits food intake in virally rescued DD mice (vrDD) as in control animals. These results indicate that the dysregulation of dopamine signaling in the dorsal striatum is sufficient to induce hypophagia and suggest that regulated release of dopamine in that brain region is essential for normal feeding and, probably, many other goal-directed behaviors.
Sotak
Bethany N
BN
Howard Hughes Medical Institute and Department of Biochemistry, University of Washington, Health Sciences Building, Room J661D, 1959 NE Pacific Street, Box 357370, Seattle, WA 98195-7370, USA.
Hnasko
Thomas S
TS
Robinson
Siobhan
S
Kremer
Erik J
EJ
Palmiter
Richard D
RD
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D004298:Dopamine / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology; D007276:Injections, Intraventricular; D007980:Levodopa / Q000494:pharmacology; D008636:Mesencephalon / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017072:Neostriatum / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D009627:Nomifensine / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D015259:Dopamine Agents; D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D009627:Nomifensine; D007980:Levodopa; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine; D004298:Dopamine