Early social isolation stress increases addiction vulnerability to heroin and alters c-Fos expression in the mesocorticolimbic system.
Early social isolation stress increases addiction vulnerability to heroin and alters c-Fos expression in the mesocorticolimbic system.
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DOI：
10.1007/s00213-021-06024-1
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发表时间：
2022-04
影响因子：
3.4
通讯作者：
Wang, Zi-Jun
中科院分区：
文献类型：
--
作者：
Singh, Archana;Xie, Yang;Davis, Ashton;Wang, Zi-Jun
关键词：
儿童早期或青少年时期的不良心理社会因素损害神经结构和脑功能，诱发许多精神疾病的易感性，如物质使用障碍。然而，早期生活压力诱导成瘾脆弱性的机制仍然不清楚，特别是阿片类药物。为了解决这个问题，我们使用小鼠海洛因自我管理模型来研究慢性早期社会隔离（ESI）压力（5周，从断奶开始）如何影响成年期对海洛因的行为和神经反应。我们发现，ESI压力并没有改变收购蔗糖或海洛因自我管理，也没有改变蔗糖的动机上的进步比例时间表。然而，ESI应激诱导雌性小鼠的海洛因剂量-反应曲线上移，并增加了动机和寻求海洛因在两种性别。此外，我们研究了中皮质边缘系统的关键脑区，包括前边缘皮质（PrL），边缘下皮质（IL），核丘脑（NAc）的核心和外壳，尾壳核和腹侧被盖区（VTA）内的神经元活动（c-Fos表达测量）。我们发现，ESI应力抑制c-Fos的表达在PrL，IL，和VTA后14天的强制禁欲，而增加的海洛因预测的背景下，提示在IL和NAc核心的神经元反应。此外，ESI应激破坏了c-Fos表达与PrL中海洛因寻求试验期间尝试输注之间的关联。这些数据表明，ESI压力导致增加寻求和动机海洛因，这可能与不同的变化，在不同的分区中皮质边缘系统的神经元活动。
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. 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. 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. 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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DOI：
10.1523/jneurosci.1914-12.2012
发表时间：
2012-08-22
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Fanous S;Goldart EM;Theberge FR;Bossert JM;Shaham Y;Hope BT
通讯作者：
Hope BT
影响因子：
3.3
作者：
Caruso, Michael J.;Crowley, Nicole A.;Kamens, Helen M.
通讯作者：
Kamens, Helen M.
影响因子：
25
作者：
Bossert, Jennifer M.;Stern, Anna L.;Theberge, Florence R. M.;Cifani, Carlo;Koya, Eisuke;Hope, Bruce T.;Shaham, Yavin
通讯作者：
Shaham, Yavin
影响因子：
3.6
作者：
Ding, YJ;Kang, L;Ma, L
通讯作者：
Ma, L
影响因子：
2.7
作者：
ANGLIN, MD;HSER, YI;MCGLOTHLIN, WH
通讯作者：
MCGLOTHLIN, WH