Journal Article

Opioid Self-Administration is Attenuated by Early-Life Experience and Gene Therapy for Anti-Inflammatory IL-10 in the Nucleus Accumbens of Male Rats

Grace, Peter M, Levin, Edward D, Wells, Corinne, Bilbo, Staci D, Hanamsagar, Richa, Lacagnina, Michael J, Kopec, Ashley M, Cox, Stewart S, Watkins, Linda R, Slade, Susan

2017

Overview

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.

• Publisher: Nature Publishing Group
• Subject: Cytokines / Deoxyribonucleic acid / DNA / Drug abuse / Drug addiction / Drug self-administration / Early experience / Food / Gene expression / Gene therapy / Inflammation / Interleukin 10 / Intravenous administration / Mental disorders / Morphine / Narcotics / Neonates / Nucleus accumbens / Opioids / Original / Reinforcement / Remifentanil / Rodents / Signal transduction / Sucrose / Transcription