TY - JOUR T1 - Vitamin D3: a role in dopamine circuit regulation, diet-induced obesity, and drug consumption JF - eneuro JO - eneuro DO - 10.1523/ENEURO.0122-15.2016 SP - ENEURO.0122-15.2016 AU - Joseph R. Trinko AU - Benjamin B. Land AU - Wojciech B. Solecki AU - Robert J. Wickham AU - Luis A. Tellez AU - Jaime Maldonado-Aviles AU - Ivan E. de Araujo AU - Nii A. Addy AU - Ralph J. DiLeone Y1 - 2016/05/06 UR - http://www.eneuro.org/content/early/2016/05/06/ENEURO.0122-15.2016.abstract N2 - 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 ip) were performed. Non-deficient 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 naïve mice, enhanced amphetamine-induced dopamine release in both naïve mice and rats, and increased locomotor activity after acute amphetamine (2.5 mg/kg, ip.). Alternatively, mice that were chronically fed either the reduced D3 high fat or chow diets displayed less activity after acute amphetamine compared to their respective controls. Finally, high fat deficient mice that were trained to orally consume liquid amphetamine (90 mg/L) displayed increased consumption, while non-deficient 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 on 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.Significance Statement: Obesity rates have risen in this country and low levels of circulating vitamin D3 correlate with high adiposity. Recent evidence suggests effects of vitamin D3 on dopamine circuits. While altered dopamine signaling has been implicated in the progression of obesity and consumption of drugs of abuse, a role for vitamin D3 in these disease states has not been experimentally explored. Using reduced dietary D3, as well as treatment with the fully active form of D3, we demonstrate effects on food and drug intake, as well as robust effects on dopamine circuits of the brain. These data suggest dopamine circuits to be a novel therapeutic target for D3 treatment with implications for obesity, drug addiction and other dopamine-dependent behaviors. ER -