Risperidone Reverses the Spatial Object Recognition Impairment and Hippocampal BDNF-TrkB Signalling System Alterations Induced by Acute MK-801 Treatment

Overview

Journal Biomed Rep

Specialty Biochemistry

Date 2017 Apr 29

PMID 28451387

Citations 4

Authors

Guangdong Chen

Xiaodong Lin

Gongying Li

Diego Jiang

Zhiruo Lib

Ronghuan Jiang

Chuanjun Zhuo

Affiliations

Soon will be listed here.

Abstract

The aim of the present study was to investigate the effects of a commonly-used atypical antipsychotic, risperidone, on alterations in spatial learning and in the hippocampal brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signalling system caused by acute dizocilpine maleate (MK-801) treatment. In experiment 1, adult male Sprague-Dawley rats subjected to acute treatment of either low-dose MK801 (0.1 mg/kg) or normal saline (vehicle) were tested for spatial object recognition and hippocampal expression levels of BDNF, TrkB and the phophorylation of TrkB (p-TrkB). We found that compared to the vehicle, MK-801 treatment impaired spatial object recognition of animals and downregulated the expression levels of p-TrkB. In experiment 2, MK-801- or vehicle-treated animals were further injected with risperidone (0.1 mg/kg) or vehicle before behavioural testing and sacrifice. Of note, we found that risperidone successfully reversed the deleterious effects of MK-801 on spatial object recognition and upregulated the hippocampal BDNF-TrkB signalling system. Collectively, the findings suggest that cognitive deficits from acute -methyl-D-aspartate receptor blockade may be associated with the hypofunction of hippocampal BDNF-TrkB signalling system and that risperidone was able to reverse these alterations.

Citing Articles

NMDA Receptors in Neurodevelopmental Disorders: Pathophysiology and Disease Models.

Tumdam R, Hussein Y, Garin-Shkolnik T, Stern S Int J Mol Sci. 2024; 25(22).

PMID: 39596430 PMC: 11594297. DOI: 10.3390/ijms252212366.

Advantages and Limitations of Animal Schizophrenia Models.

Bialon M, Wasik A Int J Mol Sci. 2022; 23(11).

PMID: 35682647 PMC: 9181262. DOI: 10.3390/ijms23115968.

Risperidone Reverses the Downregulation of BDNF in Hippocampal Neurons and MK801-Induced Cognitive Impairment in Rats.

Yu W, Zhu M, Fang H, Zhou J, Ye L, Bian W Front Behav Neurosci. 2019; 13:163.

PMID: 31396062 PMC: 6664152. DOI: 10.3389/fnbeh.2019.00163.

Treatment Responses of Cognitive Function and Plasma Asymmetric Dimethylarginine to Atypical Antipsychotic in Patients With Schizophrenia.

Yu Z, Zhao Y, Zhan J, Luo T, Xiong J, Yu B Front Psychiatry. 2019; 9:733.

PMID: 30687138 PMC: 6335386. DOI: 10.3389/fpsyt.2018.00733.

References

Waterhouse E, Xu B . New insights into the role of brain-derived neurotrophic factor in synaptic plasticity. Mol Cell Neurosci. 2009; 42(2):81-9. PMC: 2748315. DOI: 10.1016/j.mcn.2009.06.009. View

Takekita Y, Koshikawa Y, Fabbri C, Sakai S, Sunada N, Onohara A . Cognitive function and risperidone long-acting injection vs. paliperidone palmitate in schizophrenia: a 6-month, open-label, randomized, pilot trial. BMC Psychiatry. 2016; 16:172. PMC: 4884618. DOI: 10.1186/s12888-016-0883-9. View

Robinson D, Gallego J, John M, Petrides G, Hassoun Y, Zhang J . A Randomized Comparison of Aripiprazole and Risperidone for the Acute Treatment of First-Episode Schizophrenia and Related Disorders: 3-Month Outcomes. Schizophr Bull. 2015; 41(6):1227-36. PMC: 4601722. DOI: 10.1093/schbul/sbv125. View

Yu B, Wang X, Wei J, Ni P, Liang L, Zhao L . [Effect of Risperidone on BDNF-TrkB Signaling Pathway in Rat Brain]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2015; 46(4):528-32, 610. View

Keshavan M, Nasrallah H, Tandon R . Schizophrenia, "Just the Facts" 6. Moving ahead with the schizophrenia concept: from the elephant to the mouse. Schizophr Res. 2011; 127(1-3):3-13. PMC: 3391657. DOI: 10.1016/j.schres.2011.01.011. View

Bevins R, Besheer J . Object recognition in rats and mice: a one-trial non-matching-to-sample learning task to study 'recognition memory'. Nat Protoc. 2007; 1(3):1306-11. DOI: 10.1038/nprot.2006.205. View

Rogoz Z, Kaminska K . The effect of combined treatment with escitalopram and risperidone on the MK-801-induced changes in the object recognition test in mice. Pharmacol Rep. 2016; 68(1):116-20. DOI: 10.1016/j.pharep.2015.07.004. View

Lipina T, Palomo V, Gil C, Martinez A, Roder J . Dual inhibitor of PDE7 and GSK-3-VP1.15 acts as antipsychotic and cognitive enhancer in C57BL/6J mice. Neuropharmacology. 2012; 64:205-14. DOI: 10.1016/j.neuropharm.2012.06.032. View

Pandya C, Kutiyanawalla A, Pillai A . BDNF-TrkB signaling and neuroprotection in schizophrenia. Asian J Psychiatr. 2013; 6(1):22-8. PMC: 3565158. DOI: 10.1016/j.ajp.2012.08.010. View

10.

Nilsson M, Hansson S, Carlsson A, Carlsson M . Differential effects of the N-methyl-d-aspartate receptor antagonist MK-801 on different stages of object recognition memory in mice. Neuroscience. 2007; 149(1):123-30. DOI: 10.1016/j.neuroscience.2007.07.019. View

11.

Huang T . Effects of antipsychotics on the BDNF in schizophrenia. Curr Med Chem. 2012; 20(3):345-50. DOI: 10.2174/092986713804870729. View

12.

Barker G, Bird F, Alexander V, Warburton E . Recognition memory for objects, place, and temporal order: a disconnection analysis of the role of the medial prefrontal cortex and perirhinal cortex. J Neurosci. 2007; 27(11):2948-57. PMC: 6672574. DOI: 10.1523/JNEUROSCI.5289-06.2007. View

13.

Yang Y, Li Y, Wang W, Wan J, Yu B, Wang M . Small-molecule TrkB agonist 7,8-dihydroxyflavone reverses cognitive and synaptic plasticity deficits in a rat model of schizophrenia. Pharmacol Biochem Behav. 2014; 122:30-6. DOI: 10.1016/j.pbb.2014.03.013. View

14.

Corena-McLeod M . Comparative Pharmacology of Risperidone and Paliperidone. Drugs R D. 2015; 15(2):163-74. PMC: 4488186. DOI: 10.1007/s40268-015-0092-x. View

15.

Houthoofd S, Morrens M, Sabbe B . Cognitive and psychomotor effects of risperidone in schizophrenia and schizoaffective disorder. Clin Ther. 2008; 30(9):1565-89. DOI: 10.1016/j.clinthera.2008.09.014. View

16.

Lopez Hill X, Richeri A, Scorza C . Measure of anxiety-related behaviors and hippocampal BDNF levels associated to the amnesic effect induced by MK-801 evaluated in the modified elevated plus-maze in rats. Physiol Behav. 2015; 147:359-63. DOI: 10.1016/j.physbeh.2015.05.013. View

17.

Subotnik K, Casaus L, Ventura J, Luo J, Hellemann G, Gretchen-Doorly D . Long-Acting Injectable Risperidone for Relapse Prevention and Control of Breakthrough Symptoms After a Recent First Episode of Schizophrenia. A Randomized Clinical Trial. JAMA Psychiatry. 2015; 72(8):822-9. PMC: 5065351. DOI: 10.1001/jamapsychiatry.2015.0270. View

18.

Kumar V, Ahmad M, Najmi A, Akhtar M . Effect of Sarcosine (a Glycine Transport 1 Inhibitor) and Risperidone (an Atypical antipsychotic Drug) on MK-801 Induced Learning and Memory Deficits in Rats. Drug Res (Stuttg). 2015; 66(1):11-7. DOI: 10.1055/s-0035-1545299. View

19.

Kim T, Kang H, Park J, Lee S, Baek S, Kim C . Voluntary wheel running ameliorates symptoms of MK-801-induced schizophrenia in mice. Mol Med Rep. 2014; 10(6):2924-30. DOI: 10.3892/mmr.2014.2644. View

20.

Su Y, Si T, Zhou D, Guo C, Wang X, Yang Y . Risperidone attenuates MK-801-induced hyperlocomotion in mice via the blockade of serotonin 5-HT 2A/2C receptors. Eur J Pharmacol. 2007; 564(1-3):123-30. DOI: 10.1016/j.ejphar.2007.02.031. View