Sex-dependent differences in the stress mitigating and antidepressant effects of selective aryl hydrocarbon receptor modulators.
Sex-dependent differences in the stress mitigating and antidepressant effects of selective aryl hydrocarbon receptor modulators.
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选择性芳烃受体调节剂的缓解压力和抗抑郁作用存在性别依赖性差异。
DOI：
10.1016/j.jad.2022.09.155
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发表时间：
2022
影响因子：
6.6
通讯作者：
Eitan,Shoshana
中科院分区：
文献类型：
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作者：
Madison,CaitlinA;Debler,RoannaA;Vardeleon,NathanI;Hillbrick,Lauren;Jayaraman,Arul;Safe,Stephen;Chapkin,RobertS;Eitan,Shoshana
背景我们最近的研究表明，选择性芳烃受体调节剂（SAhRM），如1，4-二羟基-2-萘甲酸（DHNA），在雌性小鼠中具有抗抑郁作用。鉴于某些SAhRMs的一些影响是已知的，也是通过雌激素受体信号传导介导的，本研究探讨是否SAhRMs对情绪，情绪状态和认知的影响是sex-dependent. MethodsC 57 BL/6 N小鼠饲喂车辆或20毫克/公斤DHNA三个星期前，四周不可预测的慢性轻度应激（UCMS）。研究小鼠的抑郁样行为（蔗糖偏好、强迫游泳试验（FST）、飞溅试验、胶带梳理试验）、情绪状态（旷场试验、明/暗试验、大理石掩埋、新奇诱导的摄食量减少、高架十字迷宫）和认知结果UCMS降低了雌性大鼠的蔗糖偏好性，增加了FST不动时间;这两种作用都被DHNA阻止。在雄性中，UCMS增加了FST不动时间，并增加了在飞溅试验中的潜伏期。DHNA未减轻这些影响。然而，在男性中，UCMS诱导增加新奇诱导的运动，在L/D测试中在光室中花费的时间增加，以及在新位置与物体一起花费的时间增加。这些影响被阻止DHNA.ConclusionsOur研究结果表明，DHNA具有很高的潜力，作为抗抑郁药的女性。然而，鉴于经典解释，DHNA似乎在雄性中不起抗抑郁药的作用。尽管如此，我们的研究结果表明，DHNA可以减轻男性的压力影响和反应。
BackgroundOur recent study demonstrated that selective aryl hydrocarbon receptor modulators (SAhRMs), such as 1,4-dihydroxy-2-napthoic acid (DHNA) act as antidepressants in female mice. Given that some effects of certain SAhRMs are known to also be mediated via estrogen receptor signaling, this study examined whether the effects of SAhRMs on mood, emotional state, and cognition are sex-dependent.MethodsC57BL/6N mice were fed with vehicle or 20 mg/kg DHNA for three weeks prior to four weeks of unpredictable chronic mild stress (UCMS). Mice were examined for depression-like behaviors (sucrose preference, forced swim test (FST), splash test, tape groom test), emotional state (open-field test, light/dark test, marble burying, novelty-induced hypophagia, elevated-plus maze), and cognition (object location recognition, novel object recognition, Morris water maze).ResultsIn females, UCMS decreased sucrose preference and increased FST immobility time; both effects were prevented by DHNA. In males, UCMS increased FST immobility time, and increased the latency to groom in the splash test. These effects were not mitigated by DHNA. However, in males, UCMS induced an increase in novelty-induced locomotion, an increase in the time spent in the light compartment in the L/D test, and an increase in the time spent with an object in a novel location. These effects were prevented by DHNA.ConclusionsOur findings indicate that DHNA has high potential to act as antidepressants in females. However, given classical interpretation, DHNA did not appear to act as an antidepressant in males. Nonetheless, our findings indicate that DHNA can mitigate stress effects and reactivity in males.
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影响因子：
6.6
作者：
Madison, Caitlin A.;Kuempel, Jacob;Albrecht, Georgia Lee;Hillbrick, Lauren;Jayaraman, Arul;Safe, Stephen;Chapkin, Robert S.;Eitan, Shoshana
通讯作者：
Eitan, Shoshana
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6.7
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通讯作者：
Kasper S
影响因子：
3.8
作者：
Marques M;Laflamme L;Benassou I;Cissokho C;Guillemette B;Gaudreau L
通讯作者：
Gaudreau L
影响因子：
3.6
作者：
Marco, Eva M.;Ballesta, Javier Antonio;Viveros, Maria-Paz
通讯作者：
Viveros, Maria-Paz
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影响因子：
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作者：
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通讯作者：
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