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Ingestive Behavior and Neurosciences

Water Maze Performance in Young Male Long-Evans Rats Is Inversely Affected by Dietary Intakes of Niacin and May Be Linked to Levels of the NAD⁺ Metabolite cADPR¹

² Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada N1G 2W1 and ³ Department of Pharmacology and Toxicology and Arizona Cancer Center, University of Arizona, Tucson, AZ 85724

^* To whom correspondence should be addressed. E-mail: gyoung01{at}uoguelph.ca.

Niacin is converted in tissues to NAD⁺, which is required for synthesis of the intracellular calcium signaling molecule cyclic ADP-ribose (cADPR). cADPR is involved in many aspects of cognitive function, including long-term depression, in the hippocampus, a brain region that regulates spatial learning ability. The objective of this study was to determine whether niacin deficiency and pharmacological nicotinamide supplementation have an effect on spatial learning ability in young male Long-Evans rats as assessed by the Morris Water Maze, and whether brain NAD⁺ and cADPR are modified by dietary niacin intake. We investigated 3 models of niacin deficiency: niacin deficient (ND) vs. pair fed (PF), ND vs. partially feed restricted (PFR), and ND vs. niacin recovered (REC). ND rats showed an improvement in spatial learning ability relative to PF, PFR, and REC rats. ND rats also showed a decrease in both NAD⁺ and cADPR relative to PF and REC rats. We also investigated 1 model of pharmacological supplementation, niacin-supplemented vs. control. The niacin-supplemented group showed a small but significant spatial learning impairment relative to controls, and an increase in brain cADPR and NAD⁺. Changes in neural function related to the NAD⁺ associated calcium signaling molecule, cADPR, may be the link between diet and behavior.

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