| First Author | Kong J | Year | 2018 |
| Journal | Exp Neurol | Volume | 307 |
| Pages | 52-61 | PubMed ID | 29753648 |
| Mgi Jnum | J:271461 | Mgi Id | MGI:6271826 |
| Doi | 10.1016/j.expneurol.2018.05.010 | Citation | Kong J, et al. (2018) Nicotinamide phosphoribosyltransferase regulates cocaine reward through Sirtuin 1. Exp Neurol 307:52-61 |
| abstractText | 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 (1)H-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. Moreover, our findings reveal that the interplay between NAD biosynthesis and SIRT1 regulation may comprise a novel regulatory pathway that responds to chronic cocaine stimuli. |
