Estradiol mediates sex differences in aversion-resistant alcohol intake.
Estradiol mediates sex differences in aversion-resistant alcohol intake.
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DOI：
10.3389/fnins.2023.1282230
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发表时间：
2023
影响因子：
4.3
通讯作者：
Schank, Jesse R.
中科院分区：
文献类型：
--
作者：
Arnold, Miranda E.;Ramirez, Ellie B. Decker;Beugelsdyk, Lauren A.;Kuzolitz, M. Vitoria Siano;Jiang, Qiuyun;Schank, Jesse R.
尽管有负面后果，但饮酒是酒精使用障碍的核心症状。这可以通过将厌恶刺激与饮酒配对来在小鼠中进行建模，例如将苦味奎宁添加到酒精溶液中。如果动物在受到这种负面刺激的情况下继续饮酒，这通常被认为是厌恶性或不灵活的饮酒行为。我们实验室之前的研究发现，女性比男性更具有厌恶抵抗力，因为她们在抑制酒精摄入量之前可以耐受更高浓度的奎宁。有趣的是，我们没有观察到整个动情周期的摄入量有任何差异。关于奎宁酒精摄入期间的神经元激活模式，我们发现雄性小鼠的腹内侧前额叶皮质和后岛叶皮质表现出较高水平的激活，而雌性小鼠的腹侧被盖区表现出较高水平的激活。在这里介绍的实验中，我们进行了卵巢切除术，以进一步检查循环性激素在厌恶酒精摄入和神经元激活模式中的作用。此外，我们使用雌二醇或黄体酮的激素加反来确定哪种卵巢性激素介导厌恶性消耗。我们发现卵巢切除术减少了奎宁掺假的酒精摄入量，这表明循环性激素在这种行为中发挥了作用。我们还观察到，与假手术雌性小鼠相比，卵巢切除小鼠的腹侧被盖区神经元激活减少，并且补充雌二醇逆转了卵巢切除术对奎宁酒精摄入量的影响。结合我们之前的数据，这些发现表明循环雌二醇有助于表达厌恶性酒精摄入和 VTA 中的神经元活动。然而，由于这种行为不受动情周期的影响，我们认为这是由于这种激素的阈值水平，而不是整个动情周期中发生的波动。
Alcohol consumption despite negative consequences is a core symptom of alcohol use disorder. This can be modeled in mice by pairing aversive stimuli with alcohol consumption, such as adding the bitter tastant quinine to the alcohol solution. If an animal continues to drink alcohol despite such negative stimuli, this is typically considered aversion-resistant, or inflexible, drinking behavior. Previous studies in our lab have found that females are more aversion-resistant than males in that they tolerate higher concentrations of quinine before they suppress their alcohol intake. Interestingly, we did not observe any differences in intake across the estrous cycle. In regards to neuronal activation patterns during quinine-alcohol intake, we have found that male mice show higher levels of activation in the ventromedial prefrontal cortex and posterior insular cortex, while females show higher levels of activation in the ventral tegmental area. In the experiments presented here, we conducted ovariectomies to further examine the role of circulating sex hormones in aversion-resistant alcohol intake and neuronal activation patterns. Furthermore, we used hormonal addback of estradiol or progesterone to determine which ovarian sex hormone mediates aversion-resistant consumption. We found that ovariectomy reduced quinine-adulterated alcohol intake, demonstrating that circulating sex hormones play a role in this behavior. We also observed reduced neuronal activation in the VTA of ovariectomized mice compared to sham females, and that estradiol supplementation reversed the effect of ovariectomy on quinine-alcohol intake. Taken together with our prior data, these findings suggest that circulating estradiol contributes to the expression of aversion-resistant alcohol intake and neuronal activity in the VTA. However, since this behavior is not affected by the estrous cycle, we believe this is due to a threshold level of this hormone, as opposed to fluctuations that occur across the estrous cycle.
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DOI：
10.1111/j.1530-0277.1998.tb03950.x
发表时间：
1998-10-01
影响因子：
3.2
作者：
Roberts, AJ;Smith, AD;Koob, GF
通讯作者：
Koob, GF
影响因子：
3.4
作者：
Chen, Hu;Lasek, Amy W.
通讯作者：
Lasek, Amy W.
影响因子：
9.4
作者：
Piano, Mariann R.;Thur, Laurel A.;Phillips, Shane A.
通讯作者：
Phillips, Shane A.
影响因子：
16.6
作者：
Calipari ES;Juarez B;Morel C;Walker DM;Cahill ME;Ribeiro E;Roman-Ortiz C;Ramakrishnan C;Deisseroth K;Han MH;Nestler EJ
通讯作者：
Nestler EJ
影响因子：
3.3
作者：
Katner, Simon N.;Sentir, Alena M.;Steagall, Kevin B.;Ding, Zheng-Ming;Wetherill, Leah;Hopf, Frederic W.;Engleman, Eric A.
通讯作者：
Engleman, Eric A.