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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >In socially isolated mice, the reversal of brain allopregnanolone down-regulation mediates the anti-aggressive action of fluoxetine.
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In socially isolated mice, the reversal of brain allopregnanolone down-regulation mediates the anti-aggressive action of fluoxetine.

机译：在被社会隔离的小鼠中，脑中阿洛帕那诺酮的下调逆转介导了氟西汀的抗攻击作用。

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摘要

Social isolation (SI) of male mice lasting >4 weeks is associated with aggression toward intruders and a down-regulation of brain allopregnanolone (Allo) content. SI of female mice fails to down-regulate brain Allo content or to induce aggressiveness. Fluoxetine (Prozac in clinical use) is an S- and R-fluoxetine (FLX) mixture, which in mammals is metabolized into S- and R-norfluoxetine (NFLX). The S isomers of FLX and NFLX are more active than their respective R isomers in normalizing brain Allo down-regulation and in reducing the aggressiveness induced by SI. Thus, FLX stereospecifically reduces brain Allo down-regulation and the aggressiveness induced by SI, whereas serotonin (5-HT) uptake inhibition lacks stereospecificity. The doses of S-FLX and S-NFLX that reduce aggressiveness and Allo brain content down-regulation induced by SI are at least one order of magnitude lower than the doses that block 5-HT reuptake. Doses of imipramine that inhibit 5-HT uptake neither reduce aggressiveness nor normalize brain Allo down-regulation. We conclude that Allo brain content normalization is a better candidate than 5-HT reuptake inhibition to explain the reduction of aggressiveness elicited by S-FLX and S-NFLX.
机译：持续超过4周的雄性小鼠的社会隔离（SI）与侵略者的侵略以及脑中Allopregnanolone（Allo）含量的下调有关。雌性小鼠的SI不能下调大脑同种异体含量或诱导侵略性。氟西汀（临床使用百忧解）是一种S-和R-氟西汀（FLX）混合物，在哺乳动物中被代谢为S-和R-诺氟西汀（NFLX）。 FLX和NFLX的S异构体在归一化大脑Allo下调和减少SI诱导的侵袭性方面比其各自的R异构体更具活性。因此，FLX立体定向降低了大脑Allo下调和SI诱导的侵略性，而5-羟色胺（5-HT）摄取抑制则缺乏立体定向性。 S-FLX和S-NFLX的剂量可降低由SI诱导的侵略性和异体脑含量下调，其剂量比阻断5-HT再摄取的剂量低至少一个数量级。抑制5-HT摄取的丙咪嗪剂量既不会降低攻击性，也不会使大脑Allo下调正常化。我们得出结论，同种异体脑含量正常化比5-HT再摄取抑制是更好的候选者，以解释S-FLX和S-NFLX引起的侵略性降低。

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