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https://hdl.handle.net/2440/92388
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Type: | Journal article |
Title: | DAT isn’t all that: cocaine reward and reinforcement require Toll-like receptor 4 signaling |
Author: | Northcutt, A. Hutchinson, M. Wang, X. Baratta, M. Hiranita, T. Cochran, T. Pomrenze, M. Galer, E. Kopajtic, T. Li, C. Amat, J. Larson, G. Cooper, D. Huang, Y. O'Neill, C. Yin, H. Zahniser, N. Katz, J. Rice, K. Maier, S. et al. |
Citation: | Molecular Psychiatry, 2015; 20(12):1525-1537 |
Publisher: | Nature Publishing Group |
Issue Date: | 2015 |
ISSN: | 1359-4184 1476-5578 |
Statement of Responsibility: | A L Northcutt, M R Hutchinson, X Wang, M V Baratta, T Hiranita, T A Cochran, M B Pomrenze, E L Galer, T A Kopajtic, C M Li, J Amat, G Larson, D C Cooper, Y Huang, C E O'Neill, H Yin, N R Zahniser, J L Katz, K C Rice, S F Maier, R K Bachtell, and L R Watkins |
Abstract: | The initial reinforcing properties of drugs of abuse, such as cocaine, are largely attributed to their ability to activate the mesolimbic dopamine system. Resulting increases in extracellular dopamine in the nucleus accumbens (NAc) are traditionally thought to result from cocaine's ability to block dopamine transporters (DATs). Here we demonstrate that cocaine also interacts with the immunosurveillance receptor complex, Toll-like receptor 4 (TLR4), on microglial cells to initiate central innate immune signaling. Disruption of cocaine signaling at TLR4 suppresses cocaine-induced extracellular dopamine in the NAc, as well as cocaine conditioned place preference and cocaine self-administration. These results provide a novel understanding of the neurobiological mechanisms underlying cocaine reward/reinforcement that includes a critical role for central immune signaling, and offer a new target for medication development for cocaine abuse treatment. |
Keywords: | Ventral Tegmental Area Neuroglia Cells, Cultured Animals Mice, Inbred C3H Mice Rats Rats, Sprague-Dawley Naloxone Cocaine RNA, Messenger Narcotic Antagonists Self Administration Reward Signal Transduction Mutation Male Dopamine Plasma Membrane Transport Proteins Toll-Like Receptor 4 Interleukin-1beta Reinforcement, Psychology |
Description: | Advance online publication 3 February 2015 |
Rights: | © 2015 Macmillan Publishers Limited |
DOI: | 10.1038/mp.2014.177 |
Grant ID: | http://purl.org/au-research/grants/arc/DP110100297 |
Published version: | http://dx.doi.org/10.1038/mp.2014.177 |
Appears in Collections: | Aurora harvest 2 Physiology publications |
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