Efficacy and safety of prophylactic use of benzhexol after risperidone treatment in MK-801-induced mouse model of schizophrenia.

IF 3.5 3区医学 Q2 NEUROSCIENCES

Psychopharmacology Pub Date : 2024-11-18 DOI:10.1007/s00213-024-06716-4

Yongjie Zhong, Wenhui Wang, Miaomiao Zhang, Yitan Yao, Huanzhong Liu, Kai Zhang

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引用次数: 0

Abstract

Rationale: There is a debate about whether doctors should prophylactically use benzhexol in schizophrenic patients to reduce the occurrence of extrapyramidal side effects (EPS) after risperidone treatment.

Objectives: We conducted a prospective animal model to explore the efficacy and safety of the prophylactic use of benzhexol after risperidone treatment and the mechanism of the process.

Methods: C57/BL mice were injected with MK-801 (0.5 mg/kg, i.p.) once a day for two weeks. The open field test (OFT) and the novel object recognition test (NORT) assessed the schizophrenia-like behavior of mice. After four weeks of treatment with benzhexol (10 mg/kg, i.g.) and risperidone (3 mg/kg, i.g.), the inclined screen test (IST), rotarod test (RT), open field test (OFT), novel object recognition test (NORT) and the Morris water maze test (MWM) were conducted successively. The expression of BDNF, p-Tau, and Tau in the hippocampus was detected by Western blot assay.

Results: We showed that benzhexol can significantly attenuate risperidone-induced motor coordination impairments and catalepsy and did not affect the efficacy of risperidone in reducing spontaneous activity. Notably, the prophylactic use of benzhexol reduced the recognition memory and spatial memory in MK-801-induced model mice after risperidone. In addition, benzhexol increased the ratio of p-Tau/Tau and decreased BDNF expression levels in the hippocampus.

Conclusions: We found that the prophylactic use of benzhexol can reduce the occurrence of EPS and does not affect the efficacy of risperidone in the treatment of positive symptoms. Benzhexol may impair cognitive function but did not cause further deterioration of cognitive function in MK-801 mice.

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在 MK-801 诱导的精神分裂症小鼠模型中，利培酮治疗后预防性使用苯海索的有效性和安全性。

理由：关于医生是否应该在精神分裂症患者中预防性使用苯海索以减少利培酮治疗后锥体外系副作用（EPS）的发生存在争议：我们建立了一个前瞻性动物模型，以探讨利培酮治疗后预防性使用苯海索的有效性、安全性及其作用机制：给C57/BL小鼠注射MK-801（0.5 mg/kg，静注），每天一次，连续两周。开阔地试验（OFT）和新物体识别试验（NORT）评估小鼠的精神分裂症样行为。苯海索（10 毫克/千克，静注）和利培酮（3 毫克/千克，静注）治疗四周后，先后进行了斜屏试验（IST）、转体试验（RT）、开阔地试验（OFT）、新物体识别试验（NORT）和莫里斯水迷宫试验（MWM）。结果表明，苯海索能抑制海马中BDNF、p-Tau和Tau的表达：结果表明，苯海索能显著减轻利培酮诱导的运动协调障碍和催眠，且不影响利培酮减少自发活动的疗效。值得注意的是，预防性使用苯海索可降低利培酮诱导的 MK-801 模型小鼠的识别记忆和空间记忆。此外，苯海索增加了海马中p-Tau/Tau的比值，降低了BDNF的表达水平：我们发现，预防性使用苯海索可以减少 EPS 的发生，并且不会影响利培酮治疗阳性症状的疗效。苯海索可能会损害 MK-801 小鼠的认知功能，但不会导致认知功能进一步恶化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Psychopharmacology 医学-精神病学

CiteScore

7.10

自引率

5.90%

发文量

257

审稿时长

2-4 weeks

期刊介绍： Official Journal of the European Behavioural Pharmacology Society (EBPS) Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields: Human Psychopharmacology: Experimental This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered. Human Psychopharmacology: Clinical and Translational This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects. Preclinical psychopharmacology: Behavioral and Neural This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels. Preclinical Psychopharmacology: Translational This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways. Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.