Risperidone reverses the spatial object recognition impairment and hippocampal BDNF-TrkB signalling system alterations induced by acute MK-801 treatment

Chen,Guangdong; Lin,Xiaodong; Li,Gongying; Jiang,Diego; Lib,Zhiruo; Jiang,Ronghuan; Zhuo,Chuanjun

doi:10.3892/br.2017.850

Risperidone reverses the spatial object recognition impairment and hippocampal BDNF-TrkB signalling system alterations induced by acute MK-801 treatment

Authors:
- Guangdong Chen
- Xiaodong Lin
- Gongying Li
- Diego Jiang
- Zhiruo Lib
- Ronghuan Jiang
- Chuanjun Zhuo
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Affiliations: Department of Psychiatry, Wenzhou 7th People's Hospital, Wenzhou, Zhejiang 325000, P.R. China, College of Psychiatry, Jining Medical University, Jining, Shandong 272119, P.R. China, Department of Psychological Medicine, Chinese PLA (People's Liberation Army) Medical School, Beijing 100853, P.R. China
Published online on: January 27, 2017 https://doi.org/10.3892/br.2017.850
Pages: 285-290
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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 N‑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.

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1	Keshavan MS, Nasrallah HA and Tandon R: Schizophrenia, ‘just the facts’ 6. Moving ahead with the schizophrenia concept: From the elephant to the mouse. Schizophr Res. 127:3–13. 2011. View Article : Google Scholar : PubMed/NCBI
2	Corena-McLeod M: Comparative pharmacology of risperidone and paliperidone. Drugs R D. 15:163–174. 2015. View Article : Google Scholar : PubMed/NCBI
3	Robinson DG, Gallego JA, John M, Petrides G, Hassoun Y, Zhang JP, Lopez L, Braga RJ, Sevy SM, Addington J, et al: A randomized comparison of aripiprazole and risperidone for the acute treatment of first-episode schizophrenia and related disorders: 3-month outcomes. Schizophr Bull. 41:1227–1236. 2015. View Article : Google Scholar : PubMed/NCBI
4	Subotnik KL, Casaus LR, Ventura J, Luo JS, Hellemann GS, Gretchen-Doorly D, Marder S and Nuechterlein KH: 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. 72:822–829. 2015. View Article : Google Scholar : PubMed/NCBI
5	Kumar V, Ahmad MA, Najmi AK and 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). 66:11–17. 2016.PubMed/NCBI
6	Takekita Y, Koshikawa Y, Fabbri C, Sakai S, Sunada N, Onohara A, Nishida K, Yoshimura M, Kato M, Serretti A and Kinoshita T: Cognitive function and risperidone long-acting injection vs. paliperidone palmitate in schizophrenia: a 6-month, open-label, randomized, pilot trial. BMC Psychiatry. 16:1722016. View Article : Google Scholar : PubMed/NCBI
7	Waterhouse EG and Xu B: New insights into the role of brain-derived neurotrophic factor in synaptic plasticity. Mol Cell Neurosci. 42:81–89. 2009. View Article : Google Scholar : PubMed/NCBI
8	Pandya CD, Kutiyanawalla A and Pillai A: BDNF-TrkB signaling and neuroprotection in schizophrenia. Asian J Psychiatr. 6:22–28. 2013. View Article : Google Scholar : PubMed/NCBI
9	Huang TL: Effects of antipsychotics on the BDNF in schizophrenia. Curr Med Chem. 20:345–350. 2013. View Article : Google Scholar : PubMed/NCBI
10	Li JT, Su Y, Yang Y, Feng Z, Huang R and Si T: Effects of acute treatment of dizocilpine maleate on locomotor activity, prepulse inhibition and object recognition memory in rats. Chin J Psychiatry. 45:97–102. 2012.(In Chinese).
11	Su Y, Si T, Zhou D, Guo C and Shu L: Establishment of a schizophrenia mouse model of deficient sensorimotor gating by MK-801. Chin J Nerv Ment Dis. 32:558–560. 2006.(In Chinese).
12	Li J, Su Y, Yang Y, Feng Y, Huang RH and Si TM: The effects of low-dose MK-801 treatment on reference memory, spatial working memory and reversal learning in rats. Chin J Nerv Ment Dis. 37:261–265. 2011.(In Chinese).
13	Yang YJ, Li YK, Wang W, Wan JG, Yu B, Wang MZ and Hu B: Small-molecule TrkB agonist 7,8-dihydroxyflavone reverses cognitive and synaptic plasticity deficits in a rat model of schizophrenia. Pharmacol Biochem Behav. 122:30–36. 2014. View Article : Google Scholar : PubMed/NCBI
14	Kim TW, Kang HS, Park JK, Lee SJ, Baek SB and Kim CJ: Voluntary wheel running ameliorates symptoms of MK-801-induced schizophrenia in mice. Mol Med Rep. 10:2924–2930. 2014.PubMed/NCBI
15	Su YA, Si TM, Zhou DF, Guo CM, Wang XD, Yang Y, Shu L and Liang JH: Risperidone attenuates MK-801-induced hyperlocomotion in mice via the blockade of serotonin 5-HT 2A/2C receptors. Eur J Pharmacol. 564:123–130. 2007. View Article : Google Scholar : PubMed/NCBI
16	Barker GR, Bird F, Alexander V and Warburton EC: Recognition memory for objects, place, and temporal order: a disconnection analysis of the role of the medial prefrontal cortex and perirhinal cortex. J Neurosci. 27:2948–2957. 2007. View Article : Google Scholar : PubMed/NCBI
17	Bevins RA and Besheer J: Object recognition in rats and mice: a one-trial non-matching-to-sample learning task to study ‘recognition memory’. Nat Protoc. 1:1306–1311. 2006. View Article : Google Scholar : PubMed/NCBI
18	Lipina TV, Palomo V, Gil C, Martinez A and Roder JC: Dual inhibitor of PDE7 and GSK-3-VP1.15 acts as antipsychotic and cognitive enhancer in C57BL/6J mice. Neuropharmacology. 64:205–214. 2013. View Article : Google Scholar : PubMed/NCBI
19	Nilsson M, Hansson S, Carlsson A and Carlsson ML: Differential effects of the N-methyl-d-aspartate receptor antagonist MK-801 on different stages of object recognition memory in mice. Neuroscience. 149:123–130. 2007. View Article : Google Scholar : PubMed/NCBI
20	Rogóż Z and Kamińska 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. 68:116–120. 2016. View Article : Google Scholar : PubMed/NCBI
21	Houthoofd SA, Morrens M and Sabbe BG: Cognitive and psychomotor effects of risperidone in schizophrenia and schizoaffective disorder. Clin Ther. 30:1565–1589. 2008. View Article : Google Scholar : PubMed/NCBI
22	Hill XL, Richeri A and 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. 147:359–363. 2015. View Article : Google Scholar : PubMed/NCBI
23	Yu B, Wang X, Wei JX, Ni PY, Liang LH, Zhao LS, Ma XH, Li T and Wang YC: Effect of risperidone on the BDNF-TrkB signalling pathway in rat brain. Sichuan Da Xue Xue Bao Yi Xue Ban. 46:528–532, 610. 2015.(In Chinese). PubMed/NCBI