Multigenerational effects of adolescent morphine exposure on dopamine D2 receptor function.
Multigenerational effects of adolescent morphine exposure on dopamine D2 receptor function.
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DOI：
10.1007/s00213-012-2960-1
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发表时间：
2013-05
影响因子：
3.4
通讯作者：
Byrnes, Elizabeth M.
中科院分区：
文献类型：
--
作者：
Byrnes, John J.;Johnson, Nicole L.;Carini, Lindsay M.;Byrnes, Elizabeth M.
在过去二十年中，青少年群体，特别是青少年女性群体中处方阿片类药物的使用和滥用急剧增加。鉴于阿片类药物在神经内分泌功能中的重要作用，在这一关键发育时期接触阿片类药物可能会对雌性及其后代产生重大后果。在目前的一组研究中，我们利用雌性大鼠来模拟青春期阿片类药物暴露的跨代影响。我们研究了青春期接触吗啡的雌性成年雄性后代(F1和F2代)对多巴胺D2/D3受体激动剂奎比罗的运动敏感化反应。所有女性在受孕前至少3周内没有服用任何药物，这排除了胎儿直接接触吗啡的可能性。在重复给药后，暴露于吗啡的雌性F1和F2后代均表现出运动敏感化减弱。这些行为效应与奎比罗诱导的皮质酮分泌增加以及NAC内kappa阿片受体(KOR)和多巴胺D2受体(D2R)基因表达上调有关。这些结果表明，在青春期接触鸦片类药物的雌性后代中，D2R重复激活的反应发生了显着改变。鉴于D2R在精神病理学中的重要作用，青少年阿片类药物的暴露可能会使未来的后代更容易患上心理障碍，包括成瘾。此外，在F2代中也观察到了这种影响，这表明青少年接触阿片类药物可以触发跨代表观遗传修饰，影响对动机行为至关重要的系统。
The use and misuse of prescription opiates in adolescent populations, and in particular, adolescent female populations, has increased dramatically in the past two decades. Given the significant role that opioids play in neuroendocrine function, exposure to opiates during this critical developmental period could have significant consequences for the female, as well as her offspring. In the current set of studies, we utilized the female rat to model the transgenerational impact of adolescent opiate exposure. We examined locomotor sensitization in response to the dopamine D2/D3 receptor agonist quinpirole in the adult male progeny (F1 and F2 generation) of females exposed to morphine during adolescence. All females were drug-free for at least 3 weeks prior to conception, eliminating the possibility of direct fetal exposure to morphine. Both F1 and F2 progeny of morphine-exposed females demonstrated attenuated locomotor sensitization following repeated quinpirole administration. These behavioral effects were coupled with increased quinpirole-induced corticosterone secretion, and up-regulated kappa opioid receptor (KOR) and dopamine D2 receptor (D2R) gene expression within the NAc. These results suggest significant modifications in response to repeated D2R activation in the progeny of females exposed to opiates during adolescence. Given the significant role that the D2R plays in psychopathology, adolescent opiate exposure could shift the vulnerability of future offspring to psychological disorders, including addiction. Moreover, that effects are also observed in the F2 generation suggests that adolescent opiate exposure can trigger transgenerational epigenetic modifications impacting systems critical for motivated behavior.
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DOI：
10.1073/pnas.0610410104
发表时间：
2007-04-03
影响因子：
11.1
作者：
Crews, David;Gore, Andrea C.;Skinner, Michael K.
通讯作者：
Skinner, Michael K.
影响因子：
3.3
作者：
ORTIZ, J;DECAPRIO, JL;NESTLER, EJ
通讯作者：
NESTLER, EJ
影响因子：
4.1
作者：
de Haas, Ria;Nijdam, Annelies;Westenberg, Herman G. M.
通讯作者：
Westenberg, Herman G. M.
影响因子：
4.7
作者：
Koeltzow, TE;Austin, JD;Vezina, P
通讯作者：
Vezina, P
影响因子：
2.9
作者：
Ikemoto, S;Goeders, NE
通讯作者：
Goeders, NE