Sexually dimorphic development of the mesolimbic dopamine system is associated with nuanced sensitivity to adolescent alcohol use.
Sexually dimorphic development of the mesolimbic dopamine system is associated with nuanced sensitivity to adolescent alcohol use.
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DOI：
10.3389/fnbeh.2023.1124979
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发表时间：
2023
影响因子：
3
通讯作者：
中科院分区：
文献类型：
--
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饮酒仍然是一个主要的公共卫生问题，并且在青春期尤其普遍。青少年饮酒与晚年的一些行为异常有关，包括冒险行为和冲动的增加。因此，在动物模型中，青春期适度饮酒的雄性大鼠在成年后表现出多种影响，包括冒险行为增加、激励学习改变以及中脑边缘通路中多巴胺的更多释放。有人提出，酒精会抑制神经发育，“锁定”青少年的生理和随后的行为、表型。在这里，我们通过测试青少年发育过程中中脑边缘多巴胺的释放，检验了青少年酒精暴露后多巴胺水平升高是“锁定”表型的可行性。我们发现，在雄性大鼠中，多巴胺释放在青春期后期达到峰值，在成年期恢复到较低水平，这与青春期暴露于酒精的成年人的高多巴胺水平是由于发育停滞所致的观点一致。令人惊讶的是，女性的多巴胺释放在测试的发育窗口中保持稳定。这一结果引发了一个难题，即多巴胺水平停滞与女性的正常发育没有什么不同，因此可能不会导致病理行为。然而，上述与基于风险的决策相关的发现仅在男性受试者中进行过。当我们测试青春期饮酒的女性时，我们发现概率决策过程中的风险态度和中脑边缘多巴胺释放都没有改变。这些发现表明，不同性别的中脑边缘多巴胺系统的不同发育特征导致对酒精引起的认知和动机异常暴露的二态易感性。
Alcohol use remains a major public health concern and is especially prevalent during adolescence. Adolescent alcohol use has been linked to several behavioral abnormalities in later life, including increased risk taking and impulsivity. Accordingly, when modeled in animals, male rats that had moderate alcohol consumption during adolescence exhibit multiple effects in adulthood, including increased risk taking, altered incentive learning, and greater release of dopamine in the mesolimbic pathway. It has been proposed that alcohol arrests neural development, “locking in” adolescent physiological, and consequent behavioral, phenotypes. Here we examined the feasibility that the elevated dopamine levels following adolescent alcohol exposure are a “locked in” phenotype by testing mesolimbic dopamine release across adolescent development. We found that in male rats, dopamine release peaks in late adolescence, returning to lower levels in adulthood, consistent with the notion that high dopamine levels in adolescence-alcohol-exposed adults were due to arrested development. Surprisingly, dopamine release in females was stable across the tested developmental window. This result raised a quandary that arrested dopamine levels would not differ from normal development in females and, therefore, may not contribute to pathological behavior. However, the aforementioned findings related to risk-based decision-making have only been performed in male subjects. When we tested females that had undergone adolescent alcohol use, we found that neither risk attitude during probabilistic decision-making nor mesolimbic dopamine release was altered. These findings suggest that different developmental profiles of the mesolimbic dopamine system across sexes result in dimorphic susceptibility to alcohol-induced cognitive and motivational anomalies exposure.
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影响因子：
3.7
作者：
Clark, Jeremy J.;Nasrallah, Nicholas A.;Phillips, Paul E. M.
通讯作者：
Phillips, Paul E. M.
DOI：
10.1111/j.1530-0277.2007.00378.x
发表时间：
2007-06-01
影响因子：
3.2
作者：
Goudriaan, Anna E.;Grekin, Emily R.;Sher, Kenneth J.
通讯作者：
Sher, Kenneth J.
影响因子：
5.3
作者：
Schindler, Abigail G.;Soden, Marta E.;Clark, Jeremy J.
通讯作者：
Clark, Jeremy J.
DOI：
10.1016/j.jaac.2010.08.017
发表时间：
2010-12
影响因子：
13.3
作者：
Casey BJ;Jones RM
通讯作者：
Jones RM
影响因子：
21.1
作者：
Crews FT;Vetreno RP;Broadwater MA;Robinson DL
通讯作者：
Robinson DL