Abstract
Nuclear factor κ-light chain enhancer of activated B cells (NF-κB) is a transcription factor commonly associated with innate immunity and is activated by infection and inflammation. NF-κB has recently gained attention as a mediator of complex psychiatric phenomena such as stress and addiction. In regards to alcohol, most research on NF-κB has focused on neurotoxicity and few studies have explored the role of NF-κB in alcohol reward, reinforcement, or consumption. In these studies, we used conditioned place preference to assess the activity of NF-κB in response to rewarding doses of alcohol. To measure NF-κB activity we used a line of transgenic mice that express the LacZ gene under the control of an NF-κB-regulated promoter. In these animals, staining for β-galactosidase (β-gal) identifies cells in which NF-κB has been activated. We then used the Daun02 inactivation method to specifically silence NF-κB-expressing cells during place preference conditioning. Daun02 is an inactive prodrug that is converted to the inhibitory molecule daunorubicin by β-gal. After alcohol place conditioning, we observed increased β-gal staining in the nucleus accumbens (NAC) shell and dorsal raphe nucleus, and found that disruption of NF-κB-expressing cells using Daun02 attenuated the development of alcohol place preference when infused into the NAC shell following conditioning sessions. We found this effect to be regionally and temporally specific. These results suggest that, in addition to its role in alcohol-induced neurotoxicity, NF-κB mediates the development of alcohol place preference via its actions in the NAC shell.
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Acknowledgements
We thank Dr Scott Russo (Mt. Sinai Medical School) for providing NF-κB-LacZ breeder mice and Dr Georgia Hodes (Virginia Polytechnic Institute and State University) for breeding/genotyping advice. We thank Dr Nikolay Filipov (University of Georgia) for sharing his expertise in mouse cannulation surgery. We also thank Dr Yavin Shaham (National Institute on Drug Abuse) for thoughtful comments on our data.
Author contributions
SEN and JRS analyzed the data, prepared figures, and wrote the manuscript. SEN, JRS, CK, HDF, SHC, BMS, MKS, and JEE contributed to data collection. CL and JFC preformed the TUNEL assay. SEN, JRS, and MH contributed to the experimental design and drafting the manuscript.
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Nennig, S., Fulenwider, H., Chimberoff, S. et al. Selective Lesioning of Nuclear Factor-κB Activated Cells in the Nucleus Accumbens Shell Attenuates Alcohol Place Preference. Neuropsychopharmacol. 43, 1032–1040 (2018). https://doi.org/10.1038/npp.2017.214
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DOI: https://doi.org/10.1038/npp.2017.214
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