Kokras N, Dalla C
Department of Pharmacology, Medical School, University of Athens, Greece; First Department of Psychiatry, Eginition Hospital, Medical School, University of Athens, Greece.
Br J Pharmacol. 2014 Oct;171(20):4595-619. doi: 10.1111/bph.12710. Epub 2014 Jul 1.
Psychiatric disorders are characterized by sex differences in their prevalence, symptomatology and treatment response. Animal models have been widely employed for the investigation of the neurobiology of such disorders and the discovery of new treatments. However, mostly male animals have been used in preclinical pharmacological studies. In this review, we highlight the need for the inclusion of both male and female animals in experimental studies aiming at gender-oriented prevention, diagnosis and treatment of psychiatric disorders. We present behavioural findings on sex differences from animal models of depression, anxiety, post-traumatic stress disorder, substance-related disorders, obsessive-compulsive disorder, schizophrenia, bipolar disorder and autism. Moreover, when available, we include studies conducted across different stages of the oestrous cycle. By inspection of the relevant literature, it is obvious that robust sex differences exist in models of all psychiatric disorders. However, many times results are conflicting, and no clear conclusion regarding the direction of sex differences and the effect of the oestrous cycle is drawn. Moreover, there is a lack of considerable amount of studies using psychiatric drugs in both male and female animals, in order to evaluate the differential response between the two sexes. Notably, while in most cases animal models successfully mimic drug response in both sexes, test parameters and treatment-sensitive behavioural indices are not always the same for male and female rodents. Thus, there is an increasing need to validate animal models for both sexes and use standard procedures across different laboratories.
精神疾病在患病率、症状表现和治疗反应方面存在性别差异。动物模型已被广泛用于研究此类疾病的神经生物学以及发现新的治疗方法。然而，临床前药理学研究大多使用雄性动物。在本综述中，我们强调在旨在进行针对精神疾病的性别导向预防、诊断和治疗的实验研究中，需要纳入雄性和雌性动物。我们展示了来自抑郁症、焦虑症、创伤后应激障碍、物质相关障碍、强迫症、精神分裂症、双相情感障碍和自闭症动物模型的性别差异行为学研究结果。此外，如有可用信息，我们纳入了在发情周期不同阶段进行的研究。通过查阅相关文献，很明显在所有精神疾病模型中都存在显著的性别差异。然而，很多时候结果相互矛盾，关于性别差异的方向和发情周期的影响并未得出明确结论。此外，缺乏大量在雄性和雌性动物中使用精神科药物以评估两性间差异反应的研究。值得注意的是，虽然在大多数情况下动物模型成功模拟了两性的药物反应，但雄性和雌性啮齿动物的测试参数和对治疗敏感的行为指标并不总是相同。因此，越来越需要对两性的动物模型进行验证，并在不同实验室使用标准程序。
