Department of Physiology, School of Basic Medicine, Southwest Medical University, Luzhou, Sichuan, China; Laboratory of Nonhuman Primate Disease Modeling Research, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Laboratory of Nonhuman Primate Disease Modeling Research, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Biochem Biophys Res Commun. 2022 Jul 30;615:36-42. doi: 10.1016/j.bbrc.2022.05.041. Epub 2022 May 14.
Mental disorders are characterized by high incidence and high recurrence rates, and only part of patients responded to drug medication. In this case, substantial preclinical investigations are needed. Most antipsychotics taken daily orally in clinics are administered through injection, oral gavage, or minipum implant in rodents, which may induce stress and affect the results of behavioral tests. How drug administrations on behaviors and drug efficacy remains an unsolved problem. In this study, we compared the intraperitoneal injection (IP), intragastric administration (IG), and tail vein injection (TVI) on behaviors, as well as the difference between administration-induced stress and chronic unpredictable mild stress (CUMS). Next, we studied the effects of IG on CUMS model and drug efficacy. We found that IP, IG, and TVI, especially IG, induced a behavior-like phenotype of depression and anxiety, which we call the "CUMS-like behaviors". However, such behaviors were not equal to depression. When treated CUMS mice with saline by gavage, they didn't show any aggravated phenotype compared with CUMS alone. We observed that fluoxetine by intraperitoneal injection was more effective than intragastric administration. Our study confirmed that repeated administrations lead to CUMS-like behaviors. Although these behaviors are not depression, they have adverse effects on drug efficacy.
精神障碍的发病率和复发率都很高，只有部分患者对药物治疗有反应。在这种情况下，需要进行大量的临床前研究。临床上每天口服的大多数抗精神病药物在啮齿动物中通过注射、灌胃或微型植入物给药，这可能会引起应激反应，影响行为测试的结果。药物对行为和药效的影响仍然是一个未解决的问题。在这项研究中，我们比较了腹腔注射（IP）、灌胃和尾静脉注射（TVI）对行为的影响，以及给药引起的应激和慢性不可预测轻度应激（CUMS）之间的差异。接下来，我们研究了灌胃给药对 CUMS 模型和药效的影响。我们发现，IP、IG 和 TVI，特别是 IG，诱导出类似抑郁和焦虑的行为表型，我们称之为“CUMS 样行为”。然而，这些行为并不等同于抑郁。当用灌胃法给 CUMS 小鼠给予生理盐水时，与单独 CUMS 相比，它们没有表现出任何加重的表型。我们观察到腹腔注射氟西汀比灌胃给药更有效。我们的研究证实，重复给药会导致 CUMS 样行为。尽管这些行为不是抑郁，但它们会对药物疗效产生不利影响。
