Voluntary ethanol consumption reduces GABAergic neuroactive steroid (3α,5α)3-hydroxypregnan-20-one (3α,5α-THP) in the amygdala of the cynomolgus monkey.
Voluntary ethanol consumption reduces GABAergic neuroactive steroid (3α,5α)3-hydroxypregnan-20-one (3α,5α-THP) in the amygdala of the cynomolgus monkey.
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DOI：
10.1111/adb.12326
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发表时间：
2017-03
影响因子：
3.4
通讯作者：
Morrow AL
中科院分区：
文献类型：
--
作者：
Beattie MC;Maldonado-Devincci AM;Porcu P;O'Buckley TK;Daunais JB;Grant KA;Morrow AL
神经活性类固醇，如（3α，5 α）3-羟基甾烷-20-酮（3α，5 α-THP，别孕烯醇酮）可增强乙醇的GABA能效应，并调节啮齿动物的过量饮酒。此外，慢性乙醇消耗降低人血浆、大鼠海马和小鼠边缘区中的3α，5 α-THP水平。我们探索了食蟹猴每日自我给予乙醇12个月后边缘脑区3α，5 α-THP水平与自愿乙醇消耗量之间的关系，并进一步检查了乙醇暴露前与HPA轴功能的关系。对猴进行乙醇消耗的计划诱导，然后在12个月内每天22小时自由获取乙醇或水。用抗3α，5 α-THP抗体进行免疫组织化学。长期自愿饮酒导致乙醇消耗量的个体差异，范围为1.2 - 4.2 g/kg/天，超过12个月。长时间的酒精摄入使外侧杏仁核和基底外侧杏仁核的3α，5 α-THP免疫反应性分别降低了13±2%（p<0.05）和17±2%（p<0.05）。乙醇的影响在饮酒≥3 g/kg≥20%的重度饮酒者中最为明显。因此，外侧杏仁核和基底外侧杏仁核中的3α，5 α-THP免疫反应性与平均每日乙醇摄入量呈负相关（斯皮尔曼r分别为-0.87和-0.72，p<0.05）。然而，在基底内侧杏仁核中没有观察到乙醇的影响，也没有观察到饮酒与3α，5 α-THP免疫反应性之间的相关性。3α，5 α-THP免疫反应性与HPA轴功能相关。这些数据表明，自愿饮酒可降低非人灵长类动物杏仁核中3α，5 α-THP的水平，杏仁核3α，5 α-THP水平可能与HPA轴功能有关。
Neuroactive steroids such as (3α,5α)3-hydroxypregnan-20-one (3α,5α-THP, allopregnanolone) enhance the GABAergic effects of ethanol and modulate excessive drinking in rodents. Moreover, chronic ethanol consumption reduces 3α,5α-THP levels in human plasma, rat hippocampus, and mouse limbic regions. We explored the relationship between 3α,5α-THP levels in limbic brain areas and voluntary ethanol consumption in the cynomolgus monkey following daily self-administration of ethanol for 12 months and further examined the relationship to HPA axis function prior to ethanol exposure. Monkeys were subjected to scheduled induction of ethanol consumption followed by free access to ethanol or water for 22 hours/day over twelve months. Immunohistochemistry was performed using an anti-3α,5α-THP antibody. Prolonged voluntary drinking resulted in individual differences in ethanol consumption that ranged from 1.2 – 4.2 g/kg/day over 12 months. Prolonged ethanol consumption reduced cellular 3α,5α-THP immunoreactivity by 13±2% (p<0.05) in the lateral amygdala and 17±2% (p<0.05) in the basolateral amygdala. The effect of ethanol was most pronounced in heavy drinkers that consumed ≥3 g/kg≥20% of days. Consequently, 3α,5α-THP immunoreactivity in both the lateral and basolateral amygdala was inversely correlated with average daily ethanol intake (Spearman r = −0.87 and −0.72, respectively, p<0.05). However, no effect of ethanol and no correlation between drinking and 3α,5α-THP immunoreactivity was observed in the basomedial amygdala. 3α,5α-THP immunoreactivity following ethanol exposure was also correlated with HPA axis function prior to ethanol exposure. These data indicate that voluntary ethanol drinking reduces amygdala levels of 3α,5α-THP in nonhuman primates and that amygdala 3α,5α-THP levels may be linked to HPA axis function.