HPA axis dysfunction during morphine withdrawal in offspring of female rats exposed to opioids preconception.
HPA axis dysfunction during morphine withdrawal in offspring of female rats exposed to opioids preconception.
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DOI：
10.1016/j.neulet.2022.136479
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发表时间：
2022-03-16
影响因子：
2.5
通讯作者：
Byrnes EM
中科院分区：
文献类型：
--
作者：
Vassoler FM;Isgate SB;Budge KE;Byrnes EM
阿片类药物的使用和滥用仍然是一个重大的公共卫生问题，特别是在美国。事实上，据估计，高达10%的青少年（12-18岁）曾非法服用阿片类药物。越来越多的证据表明，这种程度的广泛阿片类药物暴露可能会对后代产生影响。利用一个成熟的雌性孕前青少年阿片类药物暴露啮齿动物模型，我们发现成年后代阿片类药物自我服用减少，同时可卡因自我服用增加。这种双向效应可能与阿片类药物戒断相关的负面影响有关，包括应激反应增强。在这项研究中，我们验证了一个假设，即在青春期暴露于吗啡的雌性成年后代与生理盐水对照的后代相比，会表现出更多的阿片类药物戒断症状。从出生后第30天（PND30）至pnd39天，雌性小鼠给予递增剂量的吗啡（5-25 mg/kg s.c）或生理盐水（1 ml/kg）。然后，它们保持至少4周的无药状态，并在PND70或之后与drug-naïve雄性交配。成年后，它们的雄性和雌性后代（称为莫尔- f1或萨尔- f1）被给予吗啡（10 mg/kg s.c），每天两次，连续5天。然后在接下来的4天内测试他们的自发戒断行为（~PND70）。在停药48小时和96小时检测杏仁核促肾上腺皮质激素释放激素（Crh）和尿皮质素3 （Ucn3）水平。48小时测量循环皮质酮。结果表明，雄性莫尔- f1比雄性萨尔- f1重，雌性之间没有基线差异。然而，在停药期间，莫尔- f1雌性动物的体重增加速度与萨尔- f1雌性动物不同。虽然在躯体戒断症状方面没有差异，但基因表达数据显示，在戒断48小时后，女性的Crh以及Ucn3和皮质酮水平均有性别特异性和时间依赖性的影响。总的来说，这些数据表明，莫尔- f1动物在戒断和应激反应方面的差异，可能有助于观察到成瘾样行为的差异。
Opioid use and abuse remain a significant public health problem, particularly in the United States. Indeed, it is estimated that up to 10% of youths (age 12–18) have taken opioids illicitly. A growing body of evidence suggests that this level of widespread opioid exposure can have effects that extend to subsequent generations. Utilizing a well-established rodent model of preconception adolescent opioid exposure in females, we found decreased opioid self-administration coupled with increased cocaine self-administration in adult offspring. This bidirectional effect may be related to negative affect associated with opioid withdrawal, including enhanced stress reactivity. In this study, we tested the hypothesis that the adult offspring of females exposed to morphine during adolescence will demonstrate increased signs of opioid withdrawal when compared to offspring of saline controls. Females were administered increasing doses of morphine (5–25 mg/kg s.c.) or saline (1 ml/kg) from postnatal day 30 (PND30)-PND39. They were then maintained drug free for a minimum of 4 weeks and mated with drug-naïve males on or after PND70. As adults, their male and female offspring (referred to as Mor-F1 or Sal-F1) were administered morphine (10 mg/kg s.c.) twice a day for 5 days. They were then tested for spontaneous withdrawal behaviors for the next 4 days (~PND70). Levels of corticotropin releasing hormone (Crh) and urocortin 3 (Ucn3) were examined in the amygdala at 48 hours and 96 hours of withdrawal. Circulating corticosterone was measured at 48 hours. Results indicate that Mor-F1 males are heavier than Sal-F1 males with no baseline differences in females. However, Mor-F1 females did not gain weight at the same rate as Sal-F1 females during withdrawal. While there were no differences in somatic withdrawal signs, gene expression data revealed a sex-specific and time-dependent effect on Crh as well as increased Ucn3 and corticosterone in females at 48hrs withdrawal. Overall, these data point to differences in withdrawal and stress reactivity in Mor-F1 animals that may contribute to observed differences in addiction-like behaviors.
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影响因子：
3.4
作者：
Byrnes, John J.;Johnson, Nicole L.;Carini, Lindsay M.;Byrnes, Elizabeth M.
通讯作者：
Byrnes, Elizabeth M.
影响因子：
4.1
作者：
Azadi, Maryam;Gompf, Heinrich S.;Azizi, Hossein
通讯作者：
Azizi, Hossein
影响因子：
3.3
作者：
Akbarabadi, Ardeshir;Sadat-Shirazi, Mitra-Sadat;Zarrindast, Mohammad-Reza
通讯作者：
Zarrindast, Mohammad-Reza
腹侧对接区域的鸦片和可塑性。
影响因子：
5
作者：
Langlois LD;Nugent FS
通讯作者：
Nugent FS
DOI：
10.1111/ejn.14060
发表时间：
2019-08
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Goldberg LR;Gould TJ
通讯作者：
Gould TJ