Nicotinamide phosphoribosyltransferase regulates cocaine reward through Sirtuin 1

Experimental Neurology
Jueying KongXiaobo Cen

Abstract

Nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme in nicotinamide adenine dinucleotide (NAD) biosynthesis in mammals, converts nicotinamide into nicotinamide mononucleotide (NMN). NMN is subsequently converted to NAD, a component that is critical for cell energy metabolism and survival. Sirtuin 1 (SIRT1), an NAD-dependent histone deacetylase, plays an important role in mediating memory and synaptic plasticity. Here, we found that NAMPT was significantly upregulated in the ventral tegmental area (VTA) of cocaine-conditioned mice. Intraperitoneal or intra-VTA injection of FK866, a specific inhibitor of NAMPT, significantly attenuated cocaine reward. However, such effects were clearly repressed by intra-VTA expression of NAMPT or supplementation with NMN. Using 1H-nuclear magnetic resonance metabolomic analysis, we found that the content of NAD and NMN were increased in the VTA of cocaine-conditioned mice; moreover, the expression of SIRT1 was also upregulated. Interestingly, the inhibitory effect of FK866 on cocaine reward was significantly weakened in Sirt1 midbrain conditional knockout mice. Our results suggest that NAMPT-mediated NAD biosynthesis may modify cocaine behavioral effects through SIRT1. Moreove...Continue Reading

Citations

May 20, 2020·Antioxidants·Nady BraidySam van Eeden
Sep 15, 2020·Pain Research & Management : the Journal of the Canadian Pain Society = Journal De La Société Canadienne Pour Le Traitement De La Douleur·Yangyang LiMingxing Zhang
Jul 29, 2021·Journal of Cellular Physiology·Qingrui ZhuanXiangwei Fu

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