title: Melanocortin 4 receptor signaling in dopamine 1 receptor neurons is required for procedural memory learning.
abstract: It is now widely recognized that exposure to palatable foods engages reward circuits that promote over-eating and facilitate the development of obesity. While the melanocortin 4 receptor (MC4R) has previously been shown to regulate food intake and energy expenditure, little is known about its role in food reward. We demonstrate that MC4R is co-expressed with the dopamine 1 receptor (D1R) in the ventral striatum. While MC4R-null mice are hyperphagic and obese, they exhibit impairments in acquisition of operant responding for a high fat reinforcement. Restoration of MC4R signaling in D1R neurons normalizes procedural learning without affecting motivation to obtain high fat diet. MC4R signaling in D1R neurons is also required for learning in a non-food-reinforced version of the cued water maze. Finally, MC4R signaling in neostriatal slices increases phosphorylation of the Thr34 residue of DARPP-32, a protein phosphatase-1 inhibitor that regulates synaptic plasticity. These data identify a novel requirement for MC4R signaling in procedural memory learning.
authors.affiliation: Department of Internal Medicine (Division of Hypothalamic Research), University of Texas Southwestern Medical Center Dallas, Dallas, TX 75390-9127, United States.
authors.forename: Huxing
authors.initials: H
authors.lastname: Cui
authors.forename: Brittany L
authors.initials: BL
authors.lastname: Mason
authors.forename: Charlotte
authors.initials: C
authors.lastname: Lee
authors.forename: Akinori
authors.initials: A
authors.lastname: Nishi
authors.forename: Joel K
authors.initials: JK
authors.lastname: Elmquist
authors.forename: Michael
authors.initials: M
authors.lastname: Lutter
mesh_terms: D000818:Animals; D003216:Conditioning, Operant / Q000502:physiology*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism*; D005260:Female; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017072:Neostriatum / Q000378:metabolism; D010766:Phosphorylation; D044105:Receptor, Melanocortin, Type 4 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D012054:Reinforcement, Psychology
chemical_list: D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C497929:Ppp1r1b protein, mouse; D044105:Receptor, Melanocortin, Type 4; D017447:Receptors, Dopamine D1