title: Vitamin D3: A Role in Dopamine Circuit Regulation, Diet-Induced Obesity, and Drug Consumption.
abstract: The influence of micronutrients on dopamine systems is not well defined. Using mice, we show a potential role for reduced dietary vitamin D3 (cholecalciferol) in promoting diet-induced obesity (DIO), food intake, and drug consumption while on a high fat diet. To complement these deficiency studies, treatments with exogenous fully active vitamin D3 (calcitriol, 10 µg/kg, i.p.) were performed. Nondeficient mice that were made leptin resistant with a high fat diet displayed reduced food intake and body weight after an acute treatment with exogenous calcitriol. Dopamine neurons in the midbrain and their target neurons in the striatum were found to express vitamin D3 receptor protein. Acute calcitriol treatment led to transcriptional changes of dopamine-related genes in these regions in naive mice, enhanced amphetamine-induced dopamine release in both naive mice and rats, and increased locomotor activity after acute amphetamine treatment (2.5 mg/kg, i.p.). Alternatively, mice that were chronically fed either the reduced D3 high fat or chow diets displayed less activity after acute amphetamine treatment compared with their respective controls. Finally, high fat deficient mice that were trained to orally consume liquid amphetamine (90 mg/L) displayed increased consumption, while nondeficient mice treated with calcitriol showed reduced consumption. Our findings suggest that reduced dietary D3 may be a contributing environmental factor enhancing DIO as well as drug intake while eating a high fat diet. Moreover, these data demonstrate that dopamine circuits are modulated by D3 signaling, and may serve as direct or indirect targets for exogenous calcitriol.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine , New Haven, Connecticut 06519.
authors.forename: Joseph R
authors.identifier: 0000-0001-9424-7191
authors.initials: JR
authors.lastname: Trinko
authors.affiliation: Department of Psychiatry, Yale University School of Medicine , New Haven, Connecticut 06519.
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Land
authors.affiliation: Department of Psychiatry, Yale University School of Medicine , New Haven, Connecticut 06519.
authors.forename: Wojciech B
authors.identifier: 0000-0002-0473-5472
authors.initials: WB
authors.lastname: Solecki
authors.affiliation: Department of Psychiatry, Yale University School of Medicine , New Haven, Connecticut 06519.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wickham
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06519; The John B. Pierce Laboratory, New Haven, Connecticut 06519.
authors.forename: Luis A
authors.identifier: 0000-0001-6448-7290
authors.initials: LA
authors.lastname: Tellez
authors.affiliation: Department of Psychiatry, Yale University School of Medicine , New Haven, Connecticut 06519.
authors.forename: Jaime
authors.initials: J
authors.lastname: Maldonado-Aviles
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06519; The John B. Pierce Laboratory, New Haven, Connecticut 06519.
authors.forename: Ivan E
authors.initials: IE
authors.lastname: de Araujo
authors.affiliation: Department of Psychiatry, Yale University School of Medicine , New Haven, Connecticut 06519.
authors.forename: Nii A
authors.initials: NA
authors.lastname: Addy
authors.affiliation: Department of Psychiatry, Yale University School of Medicine , New Haven, Connecticut 06519.
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: DiLeone
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002117:Calcitriol / Q000494:pharmacology*; D002491:Central Nervous System Agents / Q000494:pharmacology*; D002762:Cholecalciferol / Q000172:deficiency / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism; D004435:Eating / Q000187:drug effects / Q000502:physiology; D008297:Male; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D002491:Central Nervous System Agents; D002762:Cholecalciferol; D000661:Amphetamine; D002117:Calcitriol; D004298:Dopamine
keywords: dopamine; drug addiction; feeding; obesity; vitamin D