Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/133505
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dc.contributor.author | Lacagnina, M.J. | - |
dc.contributor.author | Kopec, A.M. | - |
dc.contributor.author | Cox, S.S. | - |
dc.contributor.author | Hanamsagar, R. | - |
dc.contributor.author | Wells, C. | - |
dc.contributor.author | Slade, S. | - |
dc.contributor.author | Grace, P.M. | - |
dc.contributor.author | Watkins, L.R. | - |
dc.contributor.author | Levin, E.D. | - |
dc.contributor.author | Bilbo, S.D. | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | Neuropsychopharmacology, 2017; 42(11):2128-2140 | - |
dc.identifier.issn | 0893-133X | - |
dc.identifier.issn | 1740-634X | - |
dc.identifier.uri | https://hdl.handle.net/2440/133505 | - |
dc.description.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. | - |
dc.description.statementofresponsibility | 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 | - |
dc.language.iso | en | - |
dc.publisher | Nature Publishing Group | - |
dc.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/ | - |
dc.source.uri | http://dx.doi.org/10.1038/npp.2017.82 | - |
dc.subject | Signal Transduction | - |
dc.subject | Remifentanil | - |
dc.subject.mesh | Nucleus Accumbens | - |
dc.subject.mesh | Animals | - |
dc.subject.mesh | Animals, Newborn | - |
dc.subject.mesh | Rats | - |
dc.subject.mesh | Rats, Sprague-Dawley | - |
dc.subject.mesh | Opioid-Related Disorders | - |
dc.subject.mesh | Disease Models, Animal | - |
dc.subject.mesh | Piperidines | - |
dc.subject.mesh | Mannose | - |
dc.subject.mesh | Analgesics, Opioid | - |
dc.subject.mesh | Interleukin-10 | - |
dc.subject.mesh | Cytokines | - |
dc.subject.mesh | Conditioning, Operant | - |
dc.subject.mesh | Reinforcement Schedule | - |
dc.subject.mesh | Signal Transduction | - |
dc.subject.mesh | Gene Expression Regulation | - |
dc.subject.mesh | Pregnancy | - |
dc.subject.mesh | Female | - |
dc.subject.mesh | Male | - |
dc.subject.mesh | Genetic Therapy | - |
dc.subject.mesh | Remifentanil | - |
dc.subject.mesh | Handling, Psychological | - |
dc.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 | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1038/npp.2017.82 | - |
dc.relation.grant | http://purl.org/au-research/grants/nhmrc/1054091 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Grace, P.M. [0000-0002-8999-1220] | - |
Appears in Collections: | Psychiatry publications |
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hdl_133505.pdf | Published version | 592.82 kB | Adobe PDF | View/Open |
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