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Type: Journal article
Title: Early-life experience decreases drug-induced reinstatement of morphine CPP in adulthood via microglial-specific epigenetic programming of anti-inflammatory IL-10 expression
Author: Schwarz, J.
Hutchinson, M.
Bilbo, S.
Citation: The Journal of Neuroscience, 2011; 31(49):17835-17847
Publisher: Society for Neuroscience
Issue Date: 2011
ISSN: 0270-6474
Statement of
Jaclyn M. Schwarz, Mark R. Hutchinson, and Staci D. Bilbo
Abstract: A critical component of drug addiction research involves identifying novel biological mechanisms and environmental predictors of risk or resilience to drug addiction and associated relapse. Increasing evidence suggests microglia and astrocytes can profoundly affect the physiological and addictive properties of drugs of abuse, including morphine. We report that glia within the rat nucleus accumbens (NAcc) respond to morphine with an increase in cytokine/chemokine expression, which predicts future reinstatement of morphine conditioned place preference (CPP) following a priming dose of morphine. This glial response to morphine is influenced by early-life experience. A neonatal handling paradigm that increases the quantity and quality of maternal care significantly increases baseline expression of the anti-inflammatory cytokine IL-10 within the NAcc, attenuates morphine-induced glial activation, and prevents the subsequent reinstatement of morphine CPP in adulthood. IL-10 expression within the NAcc and reinstatement of CPP are negatively correlated, suggesting a protective role for this specific cytokine against morphine-induced glial reactivity and drug-induced reinstatement of morphine CPP. Neonatal handling programs the expression of IL-10 within the NAcc early in development, and this is maintained into adulthood via decreased methylation of the IL-10 gene specifically within microglia. The effect of neonatal handling is mimicked by pharmacological modulation of glia in adulthood with ibudilast, which increases IL-10 expression, inhibits morphine-induced glial activation within the NAcc, and prevents reinstatement of morphine CPP. Taken together, we have identified a novel gene × early-life environment interaction on morphine-induced glial activation and a specific role for glial activation in drug-induced reinstatement of drug-seeking behavior.
Keywords: Nucleus Accumbens
Animals, Newborn
Rats, Sprague-Dawley
Glial Fibrillary Acidic Protein
Narcotic Antagonists
Chromatography, Liquid
Analysis of Variance
Life Change Events
Conditioning, Operant
Gene Expression Regulation
Mass Spectrometry
Extinction, Psychological
Drug-Seeking Behavior
CD11b Antigen
Handling, Psychological
Reinforcement, Psychology
Rights: Copyright © 2011 the authors. Authors grant JNeurosci a license to publish their work and copyright remains with the author. Material published from 2010 to 2014 is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License (CC-BY-NC-SA).
DOI: 10.1523/JNEUROSCI.3297-11.2011
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Physiology publications

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