A role for dopamine in feeding responses produced by orexigenic agents.
Dopamine-deficient (DD) mice become hypophagic and die of starvation by 3 to 4 weeks of age unless dopamine is restored by daily treatment with l-3-4-dihydroxyphenylalanine (l-dopa). We demonstrate here that DD mice mount qualitatively normal counter-regulatory blood glucose responses to insulin and 2-deoxy-d-glucose (2-DG). However, unlike control mice, DD mice fail to eat in response to acute glucoprivation induced by insulin or 2-DG. They also have a severely blunted response to central administration of peptide YY (PYY). Viral-mediated restoration of dopamine synthesis to the central caudate putamen (CPu) of DD mice rescues feeding and survival. However, this treatment fails to restore insulin- and 2-DG-induced feeding despite normalizing feeding in response to food deprivation and PYY. Since dopamine signaling in the CPu is not sufficient for glucoprivation-induced feeding, we propose that this feeding behavior may be mediated by dopamine in an anatomically distinct brain region.
Hnasko
Thomas S
TS
Neurobiology and Behavior Graduate Program, University of Washington, Seattle, WA 98195, USA.
Szczypka
Mark S
MS
Alaynick
William A
WA
During
Matthew J
MJ
Palmiter
Richard D
RD
D000256:Adenoviridae / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001522:Behavior, Animal; D001786:Blood Glucose / Q000378:metabolism; D003847:Deoxyglucose / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology; D004299:Dopamine beta-Hydroxylase / Q000172:deficiency / Q000235:genetics; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D005508:Food Deprivation; D005822:Genetic Vectors; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019894:Peptide YY / Q000494:pharmacology; D012844:Sincalide / Q000008:administration & dosage; D013997:Time Factors; D014161:Transduction, Genetic; D014446:Tyrosine 3-Monooxygenase / Q000172:deficiency / Q000235:genetics
D000963:Antimetabolites; D001786:Blood Glucose; D015259:Dopamine Agents; D007004:Hypoglycemic Agents; D007328:Insulin; D019894:Peptide YY; D007980:Levodopa; D003847:Deoxyglucose; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D012844:Sincalide; D004298:Dopamine