PMID- 22159099 OWN - NLM STAT- MEDLINE DCOM- 20120202 LR - 20220409 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 31 IP - 49 DP - 2011 Dec 7 TI - Early-life experience decreases drug-induced reinstatement of morphine CPP in adulthood via microglial-specific epigenetic programming of anti-inflammatory IL-10 expression. PG - 17835-47 LID - 10.1523/JNEUROSCI.3297-11.2011 [doi] AB - 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 x early-life environment interaction on morphine-induced glial activation and a specific role for glial activation in drug-induced reinstatement of drug-seeking behavior. FAU - Schwarz, Jaclyn M AU - Schwarz JM AD - Department of Psychology and Neuroscience, Duke University, Durham, North Carolina 27705, USA. jaclyn.schwarz@duke.edu FAU - Hutchinson, Mark R AU - Hutchinson MR FAU - Bilbo, Staci D AU - Bilbo SD LA - eng GR - R01 DA025978-03/DA/NIDA NIH HHS/United States GR - F32DA030136/DA/NIDA NIH HHS/United States GR - R01DA025978/DA/NIDA NIH HHS/United States GR - R01 DA025978/DA/NIDA NIH HHS/United States GR - F32 DA030136-02/DA/NIDA NIH HHS/United States GR - F32 DA030136/DA/NIDA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (CD11b Antigen) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (Narcotic Antagonists) RN - 0 (Narcotics) RN - 130068-27-8 (Interleukin-10) RN - 36B82AMQ7N (Naloxone) RN - 76I7G6D29C (Morphine) RN - W980KJ009P (Corticosterone) SB - IM MH - Analysis of Variance MH - Animals MH - Animals, Newborn MH - CD11b Antigen/genetics/metabolism MH - Chromatography, Liquid MH - Conditioning, Operant/*drug effects MH - Corticosterone/blood MH - Drug-Seeking Behavior/drug effects/physiology MH - Epigenomics MH - Extinction, Psychological/drug effects MH - Female MH - Gene Expression Regulation/drug effects MH - Glial Fibrillary Acidic Protein/genetics/metabolism MH - Handling, Psychological MH - Immunoprecipitation MH - Interleukin-10/*blood/genetics MH - *Life Change Events MH - Male MH - Mass Spectrometry MH - Microglia/drug effects/*metabolism MH - Microinjections MH - Morphine/*pharmacology MH - Naloxone/pharmacology MH - Narcotic Antagonists/pharmacology MH - Narcotics/*pharmacology MH - Nucleus Accumbens/cytology/drug effects MH - Rats MH - Rats, Sprague-Dawley MH - Reinforcement, Psychology PMC - PMC3259856 MID - NIHMS347948 EDAT- 2011/12/14 06:00 MHDA- 2012/02/03 06:00 PMCR- 2012/06/07 CRDT- 2011/12/14 06:00 PHST- 2011/12/14 06:00 [entrez] PHST- 2011/12/14 06:00 [pubmed] PHST- 2012/02/03 06:00 [medline] PHST- 2012/06/07 00:00 [pmc-release] AID - 31/49/17835 [pii] AID - 3742323 [pii] AID - 10.1523/JNEUROSCI.3297-11.2011 [doi] PST - ppublish SO - J Neurosci. 2011 Dec 7;31(49):17835-47. doi: 10.1523/JNEUROSCI.3297-11.2011.