Enduring disruption of reward and stress circuit activities by early-life adversity in male rats.
Enduring disruption of reward and stress circuit activities by early-life adversity in male rats.
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DOI：
10.1038/s41398-022-01988-w
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发表时间：
2022-06-16
影响因子：
6.8
通讯作者：
Mahler, Stephen V.
中科院分区：
文献类型：
--
作者：
Levis, Sophia C.;Birnie, Matthew T.;Bolton, Jessica L.;Perrone, Christina R.;Montesinos, Johanna S.;Baram, Tallie Z.;Mahler, Stephen V.
在人类中，早期生活逆境（ELA），如创伤，贫困和混乱的环境与晚年情绪障碍（包括抑郁症和药物滥用）的风险增加有关。这些疾病涉及潜在的奖励回路中断，可能因性别而异。因此，我们以前发现，ELA导致雄性啮齿动物对自然奖励和可卡因的快感缺乏，而在雌性啮齿动物中，ELA反而增加了对阿片类药物和可口食物成瘾的脆弱性。虽然这些研究结果表明，ELA诱导的奖励电路中断可能会因性别而异，但对ELA在任何性别中影响的特定电路节点仍然知之甚少。在这里，在成年雄性Sprague-Dawley大鼠中，我们询问ELA如何影响我们先前在雌性ELA后测试的阿片类药物成瘾相关行为。我们通过评估阿片类药物相关的神经元激活的压力和奖励电路节点，包括杏仁核（NAc），杏仁核，内侧前额叶皮层（mPFC），和室旁丘脑探测男性潜在的电路机制。我们发现，ELA减少阿片类药物寻求行为的男性，并改变海洛因诱导的激活NAC，PFC和杏仁核，这表明一个潜在的电路为基础的机制。这些研究表明，ELA导致的行为和神经生物学破坏与雄性啮齿动物的快感缺乏一致，不像我们以前在雌性中看到的阿片类药物寻求增加。我们的研究结果，再加上我们以前的工作，表明男性和女性可能面临不同的心理健康后果ELA，这可能是必要的个性化定制未来的干预策略。
In humans, early-life adversity (ELA) such as trauma, poverty, and chaotic environment is linked to increased risk of later-life emotional disorders including depression and substance abuse. These disorders involve underlying disruption of reward circuits and likely vary by sex. Accordingly, we previously found that ELA leads to anhedonia for natural rewards and cocaine in male rodents, whereas in females ELA instead increases vulnerability to addiction-like use of opioid drugs and palatable food. While these findings suggest that ELA-induced disruption of reward circuitry may differ between the sexes, the specific circuit nodes that are influenced by ELA in either sex remain poorly understood. Here, in adult male Sprague-Dawley rats, we ask how ELA impacts opioid addiction-relevant behaviors that we previously tested after ELA in females. We probe potential circuit mechanisms in males by assessing opioid-associated neuronal activation in stress and reward circuit nodes including nucleus accumbens (NAc), amygdala, medial prefrontal cortex (mPFC), and paraventricular thalamus. We find that ELA diminishes opioid-seeking behaviors in males, and alters heroin-induced activation of NAc, PFC, and amygdala, suggesting a potential circuit-based mechanism. These studies demonstrate that ELA leads to behavioral and neurobiological disruptions consistent with anhedonia in male rodents, unlike the increased opioid seeking we previously saw in females. Our findings, taken together with our prior work, suggest that men and women could face qualitatively different mental health consequences of ELA, which may be essential for individually tailoring future intervention strategies.
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影响因子：
--
作者：
al'Absi, Mustafa
通讯作者：
al'Absi, Mustafa
DOI：
10.1111/ejn.12866
发表时间：
2015-05
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Bentzley BS;Aston-Jones G
通讯作者：
Aston-Jones G
影响因子：
15.9
作者：
Der-Avakian A;Markou A
通讯作者：
Markou A
DOI：
10.1038/npp.2009.187
发表时间：
2010-02
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.4
作者：
Bentzley, Brandon S.;Fender, Kimberly M.;Aston-Jones, Gary
通讯作者：
Aston-Jones, Gary