Depression-like behavior of aged male and female mice is ameliorated with administration of testosterone or its metabolites.
Depression-like behavior of aged male and female mice is ameliorated with administration of testosterone or its metabolites.
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DOI：
10.1016/j.physbeh.2009.02.022
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发表时间：
2009-05-25
影响因子：
2.9
通讯作者：
Walf, Alicia A.
中科院分区：
文献类型：
--
作者：
Frye, Cheryl A.;Walf, Alicia A.
关键词：
男性和女性迟发性抑郁症可能与年龄相关的雄激素产生和/或其代谢下降有关。因此，睾酮(T)及其代谢物的抗抑郁作用引起了人们的兴趣。鉴于这些雄激素具有不同的作用机制，在老年动物模型中开始描述和比较它们的作用是很重要的。我们假设老年小鼠的抑郁行为存在性别差异，雄激素会减少强迫游泳试验中的抑郁样行为。为了研究这一点，雄性和雌性小鼠（~24月龄）皮下注射T，或其5α-还原代谢物之一（二氢睾酮- DHT， 5α-雄甾烷，17β-二醇-3α-二醇），或芳香代谢物（雌二醇- E2），或油载体。小鼠在抑郁动物模型强迫游泳试验前1小时给予雄激素（1 mg/kg）。我们发现，与雌性相比，雄性一动不动的时间更长，游泳的时间更少。给药T、二氢睾酮或3α-二醇同样减少了雄性和雌性小鼠静止不动的时间，增加了挣扎的时间。E2与车辆管理相比，减少了雄性和雌性小鼠的静止时间，但增加了雌性小鼠的游泳时间和雄性小鼠的挣扎时间。总之，这些数据表明，T及其5α-还原和芳香化代谢物在老年雄性和雌性小鼠中具有抗抑郁样作用。
There may be a role of age-related decline in androgen production and/or its metabolism for late-onset depression disorders of men and women. Thus, the antidepressant-like effects of testosterone (T) and its metabolites are of interest. Given that these androgens have disparate mechanisms of action, it is important to begin to characterize and compare their effects in an aged animal model. We hypothesized that there would be sex differences in depression behavior of aged mice and that androgens would reduce depression-like behaviors in the forced swim test. To investigate this, male and female mice (~24 months old) were subcutaneously administered T, or one of its 5α-reduced metabolites (dihydrotesterone- DHT, 5α-androstane,17β-diol-3α-diol), or aromatized metabolite (estradiol- E2), or oil vehicle. Mice were administered androgens (1 mg/kg) 1 hour before being tested in the forced swim test, an animal model of depression. We found that males spent more time immobile, and less time swimming, than females. Administration of T, DHT, or 3α-diol similarly reduced time spent immobile, and increased time spent struggling, of male and female mice. E2, compared to vehicle-administration, decreased time spent immobile of males and females, but increased time spent swimming of females and time spent struggling of male mice. Together, these data suggest that T and its 5α-reduced and aromatized metabolites have anti-depressant-like effects in aged male and female mice.
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影响因子：
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