Department of Pharmacology, Medical School, University of Athens, Athens, Greece.
Basic Clin Pharmacol Toxicol. 2010 Mar;106(3):226-33. doi: 10.1111/j.1742-7843.2009.00516.x. Epub 2009 Dec 30.
Many stress-related mental disorders, including depression and post-traumatic stress disorder occur more often in women than in men. While social and cultural factors certainly contribute to these differences, neurobiological sex differences seem to also play an important role. A rapidly burgeoning literature from basic and clinical research documents sex differences in brain anatomy, chemistry and function, as well as in stress and drug responses. For example, some clinical studies have reported that women may have a better outcome when treated with selective serotonin re-uptake inhibitors, in comparison to tricyclic antidepressants. Furthermore, relatively limited basic research has been devoted to developing animal models and consequently describing drug treatments which are sensitive to sex differences. In this MiniReview, we discuss sex differences in behavioural aspects, as well as neurochemical, neurobiological and pharmacological findings that we have collected from several different animal models and tests of depression. These are the forced swim test, the chronic mild stress and the learned helplessness models, the Flinders sensitive line rats, which is a genetic model of depression and the lipopolysaccharide-induced sickness behaviour, a putative inflammatory model of depression. Collectively, our data have shown that in all animal models assayed, serotonergic neurochemical responses were differently affected in males and females, ultimately producing sex-dependent behavioural effects. In addition, Flinders sensitive line rats exhibited a sexually dimorphic response to chronic antidepressant treatment. These sex-differentiated neurochemical and behavioural alterations lend support to a major role of serotonin in the mediation of sexually dimorphic responses.
许多与压力相关的精神障碍，包括抑郁症和创伤后应激障碍，在女性中的发病率高于男性。虽然社会和文化因素肯定促成了这些差异，但神经生物学上的性别差异似乎也起着重要作用。基础和临床研究的大量新兴文献记录了大脑解剖结构、化学和功能方面的性别差异，以及应激和药物反应方面的性别差异。例如，一些临床研究报告称，与三环类抗抑郁药相比，女性在接受选择性 5-羟色胺再摄取抑制剂治疗时可能会有更好的效果。此外，相对有限的基础研究致力于开发动物模型，因此描述对性别差异敏感的药物治疗方法。在这篇综述中，我们讨论了行为方面以及神经化学、神经生物学和药理学方面的性别差异，这些差异是我们从几种不同的抑郁动物模型和测试中收集到的。这些模型包括强迫游泳测试、慢性轻度应激和习得性无助模型、弗林德斯敏感线大鼠（一种抑郁症的遗传模型）以及脂多糖诱导的疾病行为（一种潜在的抑郁症炎症模型）。总的来说，我们的数据表明，在所有测试的动物模型中，血清素能神经化学反应在男性和女性中受到不同的影响，最终产生性别依赖的行为效应。此外，弗林德斯敏感线大鼠对慢性抗抑郁治疗表现出性别二态性反应。这些性别分化的神经化学和行为改变支持了 5-羟色胺在介导性别二态反应中的重要作用。
