Effects of the dopamine depleting agent tetrabenazine in tests evaluating different components of depressive-like behavior in mice: sex-dependent response to antidepressant drugs with SERT and DAT blocker profiles.
Effects of the dopamine depleting agent tetrabenazine in tests evaluating different components of depressive-like behavior in mice: sex-dependent response to antidepressant drugs with SERT and DAT blocker profiles.
复制标题
DOI：
10.1007/s00213-023-06412-9
复制
发表时间：
2023-08
影响因子：
3.4
通讯作者：
Correa, Merce
中科院分区：
文献类型：
--
作者：
Carratala-Ros, Carla;Martinez-Verdu, Andrea;Olivares-Garcia, Regulo;Salamone, John D.;Correa, Merce
抑郁症在女性中的发病率是男性的两倍。对这种疾病的诊断和治疗反应存在性别差异。行为激活障碍（即运动障碍，疲劳）经常出现在抑郁症患者中，并且对治疗具有高度抵抗性。中脑边缘多巴胺（mesolimbic dopamine，DA）在调节雄性啮齿类动物行为激活中的作用已被广泛研究，但在雌性啮齿类动物中却知之甚少。本研究评估了用于研究抑郁样行为不同组成部分的啮齿动物范例中的潜在性别差异，以及对具有不同作用机制的抗抑郁药的治疗反应。雄性和雌性CD 1小鼠接受丁苯那嗪（TBZ），这是一种VMAT-2阻滞剂，可消耗DA并诱导人类抑郁症状。对小鼠进行强迫游泳试验（FST）、暗光箱（DL）、高架十字迷宫（EFL）、社会互动（SI）试验以及使用两瓶试验的蔗糖偏好和消耗试验。此外，安非他酮（DA再摄取抑制剂）或氟西汀（5-羟色胺再摄取抑制剂）被用来逆转TBZ诱导的运动障碍。在FST中，安非他酮逆转了TBZ对两种性别小鼠的影响，但氟西汀仅对雌性小鼠有效。DA耗竭不影响抑郁症的其他方面，如焦虑，社交或蔗糖消耗，并没有与安非他酮对这些参数的相互作用。在TBZ治疗的女性中，SERT阻断剂可能有效地逆转了在厌恶环境（FST）中的运动障碍，并增强了对焦虑刺激的回避。前多巴胺能抗抑郁药似乎更有效地改善两种性别比SERT阻滞剂的运动障碍。
Depression is a disorder twice as common in women than in men. There are sex differences in the symptomatology and treatment response to this disorder. Impairments in behavioral activation (i.e. anergia, fatigue) are often seen in people with depression and are highly resistant to treatment. The role of mesolimbic dopamine (DA) in regulating behavioral activation has been extensively studied in male rodents, but little is known in female rodents. The present studies assessed potential sex differences in rodent paradigms used to study different components of depressive-like behavior, and in the treatment response to antidepressants with different mechanisms of action. Male and female CD1 mice received Tetrabenazine (TBZ), a VMAT-2 blocker that depletes DA and induces depressive symptoms in humans. Mice were tested on the Forced Swim Test, (FST), the Dark–Light box (DL), the elevated plus maze (EPM), Social Interaction (SI) test, and sucrose preference and consumption using the two bottles test. In addition, bupropion (a DA reuptake inhibitor) or fluoxetine (a serotonin reuptake inhibitor) were used to reverse TBZ-induced anergia. In the FST, bupropion reversed TBZ effects in both sexes but fluoxetine was only effective in female mice. DA depletion did not affect other aspects of depression such as anxiety, sociability or sucrose consumption, and there was no interaction with bupropion on these parameters. In TBZ treated-females SERT-blockers may be effective at reversing anergia in aversive contexts (FST), and potentiating avoidance of anxiogenic stimuli. Pro-dopaminergic antidepressants seem more efficacious at improving anergia in both sexes than SERT-blockers.
登录
查看更多内容
影响因子：
3
作者：
López-Cruz L;San-Miguel N;Bayarri P;Baqi Y;Müller CE;Salamone JD;Correa M
通讯作者：
Correa M
影响因子：
2.6
作者：
Frank S
通讯作者：
Frank S
影响因子：
3
作者：
Carratala-Ros, Carla;Lopez-Cruz, Laura;Correa, Merce
通讯作者：
Correa, Merce
影响因子：
3.2
作者：
GUY, AP;GARDNER, CR
通讯作者：
GARDNER, CR
影响因子：
1.6
作者：
Correa, Merce;Pardo, Marta;Salamone, John D.
通讯作者：
Salamone, John D.