Early social isolation stress increases addiction vulnerability to heroin and alters c-Fos expression in the mesocorticolimbic system

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Issue Date
2022-01-08Author
Singh, Archana
Xie, Yang
Davis, Ashton
Wang, Zi-Jun
Publisher
Springer
Type
Article
Article Version
Scholarly/refereed, author accepted manuscript
Rights
Copyright © 2022, The Author(s), under exclusive license to Springer-Verlag GmbH Germany, part of Springer Nature.
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Show full item recordAbstract
Rationale
Adverse psychosocial factors during early childhood or adolescence compromise neural structure and brain function, inducing susceptibility for many psychiatric disorders such as substance use disorder. Nevertheless, the mechanisms underlying early life stress-induced addiction vulnerability is still unclear, especially for opioids.Objectives
To address this, we used a mouse heroin self-administration model to examine how chronic early social isolation (ESI) stress (5 weeks, beginning at weaning) affects the behavioral and neural responses to heroin during adulthood.Results
We found that ESI stress did not alter the acquisition for sucrose or heroin self-administration, nor change the motivation for sucrose on a progressive ratio schedule. However, ESI stress induced an upward shift of heroin dose-response curve in female mice and increased motivation and seeking for heroin in both sexes. Furthermore, we examined the neuronal activity (measured by c-Fos expression) within the key brain regions of the mesocorticolimbic system, including the prelimbic cortex (PrL), infralimbic cortex (IL), nucleus accumbens (NAc) core and shell, caudate putamen, and ventral tegmental area (VTA). We found that ESI stress dampened c-Fos expression in the PrL, IL, and VTA after 14-day forced abstinence, while augmented the neuronal responses to heroin-predictive context and cue in the IL and NAc core. Moreover, ESI stress disrupted the association between c-Fos expression and attempted infusions during heroin-seeking test in the PrL.Conclusions
These data indicate that ESI stress leads to increased seeking and motivation for heroin, and this may be associated with distinct changes in neuronal activities in different subregions of the mesocorticolimbic system.
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- Pharmacy Scholarly Works [293]
Citation
Singh, A., Xie, Y., Davis, A. et al. Early social isolation stress increases addiction vulnerability to heroin and alters c-Fos expression in the mesocorticolimbic system. Psychopharmacology 239, 1081–1095 (2022). https://doi.org/10.1007/s00213-021-06024-1
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