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• W2608882114 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 morphine-induced 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." @default.
• W2608882114 created "2017-05-05" @default.
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• W2608882114 date "2017-04-24" @default.
• W2608882114 modified "2023-10-14" @default.
• W2608882114 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" @default.
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• W2608882114 doi "https://doi.org/10.1038/npp.2017.82" @default.
• W2608882114 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5603817" @default.
• W2608882114 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28436446" @default.
• W2608882114 hasPublicationYear "2017" @default.
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