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

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

  • Psychopharmacology (Berl). 2024 Nov 18. doi: 10.1007/s00213-024-06716-4.
Yongjie Zhong # 1 2,  Wenhui Wang # 1 2,  Miaomiao Zhang # 1 2,  Yitan Yao # 1 3 4,  Huanzhong Liu 5 6 7 8,  Kai Zhang 9 10 11 12
Affiliations

Affiliations

  • 1 Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, 238000, China.
  • 2 Department of Psychiatry, School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, China.
  • 3 Anhui Psychiatric Center, Anhui Medical University, Hefei, China.
  • 4 Anhui Provincial Key Laboratory for Brain Bank Construction and Resource Utilization, Hefei, China.
  • 5 Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, 238000, China. huanzhongliu@ahmu.edu.cn.
  • 6 Department of Psychiatry, School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, China. huanzhongliu@ahmu.edu.cn.
  • 7 Anhui Psychiatric Center, Anhui Medical University, Hefei, China. huanzhongliu@ahmu.edu.cn.
  • 8 Anhui Provincial Key Laboratory for Brain Bank Construction and Resource Utilization, Hefei, China. huanzhongliu@ahmu.edu.cn.
  • 9 Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, 238000, China. zhangkai@ahmu.edu.cn.
  • 10 Department of Psychiatry, School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, China. zhangkai@ahmu.edu.cn.
  • 11 Anhui Psychiatric Center, Anhui Medical University, Hefei, China. zhangkai@ahmu.edu.cn.
  • 12 Anhui Provincial Key Laboratory for Brain Bank Construction and Resource Utilization, Hefei, China. zhangkai@ahmu.edu.cn.
  • # Contributed equally.
PMID: 39551830 DOI: 10.1007/s00213-024-06716-4
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.

Keywords

Benzhexol; Brain-derived neurotrophic factor; Extrapyramidal symptoms; MK-801; Prophylactic use; Risperidone; Schizophrenia.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z