Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/133505
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Type: | Journal article |
Title: | Opioid Self-Administration is Attenuated by Early-Life Experience and Gene Therapy for Anti-Inflammatory IL-10 in the Nucleus Accumbens of Male Rats |
Author: | Lacagnina, M.J. Kopec, A.M. Cox, S.S. Hanamsagar, R. Wells, C. Slade, S. Grace, P.M. Watkins, L.R. Levin, E.D. Bilbo, S.D. |
Citation: | Neuropsychopharmacology, 2017; 42(11):2128-2140 |
Publisher: | Nature Publishing Group |
Issue Date: | 2017 |
ISSN: | 0893-133X 1740-634X |
Statement of Responsibility: | Michael J Lacagnina, Ashley M Kopec, Stewart S Cox, Richa Hanamsagar, Corinne Wells, Susan Slade, Peter M Grace, Linda R Watkins, Edward D Levin, and Staci D Bilbo |
Abstract: | Early-life conditions can contribute to the propensity for developing neuropsychiatric disease, including substance abuse disorders. However, the long-lasting mechanisms that shape risk or resilience for drug addiction remain unclear. Previous work has shown that a neonatal handling procedure in rats (which promotes enriched maternal care) attenuates morphine conditioning, reduces morphineinduced glial activation, and increases microglial expression of the anti-inflammatory cytokine interleukin-10 (IL-10). We thus hypothesized that anti-inflammatory signaling may underlie the effects of early-life experience on later-life opioid drug-taking. Here we demonstrate that neonatal handling attenuates intravenous self-administration of the opioid remifentanil in a drug-concentration-dependent manner. Transcriptional profiling of the nucleus accumbens (NAc) from handled rats following repeated exposure to remifentanil reveals a suppression of pro-inflammatory cytokine and chemokine gene expression, consistent with an anti-inflammatory phenotype. To determine if anti-inflammatory signaling alters drug-taking behavior, we administered intracranial injections of plasmid DNA encoding IL-10 (pDNA-IL-10) into the NAc of non-handled rats. We discovered that pDNA-IL-10 treatment reduces remifentanil self-administration in a drug-concentration-dependent manner, similar to the effect of handling. In contrast, neither handling nor pDNA-IL-10 treatment alters self-administration of food or sucrose rewards. These collective observations suggest that neuroimmune signaling mechanisms in the NAc are shaped by early-life experience and may modify motivated behaviors for opioid drugs. Moreover, manipulation of the IL-10 signaling pathway represents a novel approach for influencing opioid reinforcement. |
Keywords: | Signal Transduction Remifentanil |
Rights: | © The Author(s) 2017 This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ |
DOI: | 10.1038/npp.2017.82 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1054091 |
Published version: | http://dx.doi.org/10.1038/npp.2017.82 |
Appears in Collections: | Psychiatry publications |
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