气候变化领域集成服务门户(CCPortal): Early life adversity promotes resilience to opioid addiction-related phenotypes in male rats and sex-specific transcriptional changes

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DOI	10.1073/pnas.2020173118
	Early life adversity promotes resilience to opioid addiction-related phenotypes in male rats and sex-specific transcriptional changes
	Sanchez E.O.; Bavley C.C.; Deutschmann A.U.; Carpenter R.; Peterson D.R.; Karbalaei R.; Flowers J.; II; Rogers C.M.; Langrehr M.G.; Ardekani C.S.; Famularo S.T.; Bongiovanni A.R.; Knouse M.C.; Floresco S.B.; Briand L.A.; Wimmer M.E.; Bangasser D.A.
发表日期	2021
ISSN	00278424
卷号	118 期号:8
英文摘要	Experiencing some early life adversity can have an “inoculating” effect that promotes resilience in adulthood. However, the mechanisms underlying stress inoculation are unknown, and animal models are lacking. Here we used the limited bedding and nesting (LBN) model of adversity to evaluate stress inoculation of addiction-related phenotypes. In LBN, pups from postnatal days 2 to 9 and their dams were exposed to a low-resource environment. In adulthood, they were tested for addiction-like phenotypes and compared to rats raised in standard housing conditions. High levels of impulsivity are associated with substance abuse, but in males, LBN reduced impulsive choice compared to controls. LBN males also self-administered less morphine and had a lower breakpoint on a progressive ratio reinforcement schedule than controls. These effects of LBN on addiction-related behaviors were not found in females. Because the nucleus accumbens (NAc) mediates these behaviors, we tested whether LBN altered NAc physiology in drug-naïve and morphine-exposed rats. LBN reduced the frequency of spontaneous excitatory postsynaptic currents in males, but a similar effect was not observed in females. Only in males did LBN prevent a morphine-induced increase in the AMPA/NMDA ratio. RNA sequencing was performed to delineate the molecular signature in the NAc associated with LBN-derived phenotypes. LBN produced sex-specific changes in transcription, including in genes related to glutamate transmission. Collectively, these studies reveal that LBN causes a male-specific stress inoculation effect against addiction-related phenotypes. Identifying factors that promote resilience to addiction may reveal novel treatment options for patients. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Nucleus accumbens; Sex difference; Stress; Substance use disorder; Transcription
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180562
作者单位	Department of Psychology and Neuroscience Program, Temple University, Philadelphia, PA 19122, United States; Psychology Department and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
推荐引用方式 GB/T 7714	Sanchez E.O.,Bavley C.C.,Deutschmann A.U.,et al. Early life adversity promotes resilience to opioid addiction-related phenotypes in male rats and sex-specific transcriptional changes[J],2021,118(8).
APA	Sanchez E.O..,Bavley C.C..,Deutschmann A.U..,Carpenter R..,Peterson D.R..,...&Bangasser D.A..(2021).Early life adversity promotes resilience to opioid addiction-related phenotypes in male rats and sex-specific transcriptional changes.Proceedings of the National Academy of Sciences of the United States of America,118(8).
MLA	Sanchez E.O.,et al."Early life adversity promotes resilience to opioid addiction-related phenotypes in male rats and sex-specific transcriptional changes".Proceedings of the National Academy of Sciences of the United States of America 118.8(2021).