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DAT isn’t all that: cocaine reward and reinforcement requires Toll Like Receptor 4 signaling
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523496/ https://www.ncbi.nlm.nih.gov/pubmed/25644383 http://dx.doi.org/10.1038/mp.2014.177 |
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author | Northcutt, A.L. Hutchinson, M.R. Wang, X. Baratta, M.V. Hiranita, T. Cochran, T.A. Pomrenze, M.B. Galer, E.L. Kopajtic, T.A. Li, C.M. Amat, J. Larson, G. Cooper, D.C. Huang, Y. O’Neill, C.E. Yin, H. Zahniser, N.R. Katz, J.L. Rice, K.C. Maier, S.F. Bachtell, R.K. Watkins, L.R. |
author_facet | Northcutt, A.L. Hutchinson, M.R. Wang, X. Baratta, M.V. Hiranita, T. Cochran, T.A. Pomrenze, M.B. Galer, E.L. Kopajtic, T.A. Li, C.M. Amat, J. Larson, G. Cooper, D.C. Huang, Y. O’Neill, C.E. Yin, H. Zahniser, N.R. Katz, J.L. Rice, K.C. Maier, S.F. Bachtell, R.K. Watkins, L.R. |
author_sort | Northcutt, A.L. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4523496 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-45234962016-05-18 DAT isn’t all that: cocaine reward and reinforcement requires Toll Like Receptor 4 signaling Northcutt, A.L. Hutchinson, M.R. Wang, X. Baratta, M.V. Hiranita, T. Cochran, T.A. Pomrenze, M.B. Galer, E.L. Kopajtic, T.A. Li, C.M. Amat, J. Larson, G. Cooper, D.C. Huang, Y. O’Neill, C.E. Yin, H. Zahniser, N.R. Katz, J.L. Rice, K.C. Maier, S.F. Bachtell, R.K. Watkins, L.R. Mol Psychiatry Article 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. 2015-02-03 2015-12 /pmc/articles/PMC4523496/ /pubmed/25644383 http://dx.doi.org/10.1038/mp.2014.177 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Northcutt, A.L. Hutchinson, M.R. Wang, X. Baratta, M.V. Hiranita, T. Cochran, T.A. Pomrenze, M.B. Galer, E.L. Kopajtic, T.A. Li, C.M. Amat, J. Larson, G. Cooper, D.C. Huang, Y. O’Neill, C.E. Yin, H. Zahniser, N.R. Katz, J.L. Rice, K.C. Maier, S.F. Bachtell, R.K. Watkins, L.R. DAT isn’t all that: cocaine reward and reinforcement requires Toll Like Receptor 4 signaling |
title | DAT isn’t all that: cocaine reward and reinforcement requires Toll Like Receptor 4 signaling |
title_full | DAT isn’t all that: cocaine reward and reinforcement requires Toll Like Receptor 4 signaling |
title_fullStr | DAT isn’t all that: cocaine reward and reinforcement requires Toll Like Receptor 4 signaling |
title_full_unstemmed | DAT isn’t all that: cocaine reward and reinforcement requires Toll Like Receptor 4 signaling |
title_short | DAT isn’t all that: cocaine reward and reinforcement requires Toll Like Receptor 4 signaling |
title_sort | dat isn’t all that: cocaine reward and reinforcement requires toll like receptor 4 signaling |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523496/ https://www.ncbi.nlm.nih.gov/pubmed/25644383 http://dx.doi.org/10.1038/mp.2014.177 |
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