Ranitidine reduced levodopa-induced dyskinesia by remodeling neurochemical changes in hemiparkinsonian model of rats

Hongjuan Shi,1,2,* Xinxin Yang,2,3,* Hui Zhao,4 Shenyang Zhang,2 Jie Zu,2 Wei Zhang,2 Xia Shen,2 Guiyun Cui,2,3 Fang Hua,2,3 Chuanzhu Yan1 1Department of Neurology, Qilu Hospital of Shangdong University, Jinan, 2Department of Neurology, Affiliated Hospital of Xuzhou Medical College, 3Institute of N...

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Autores principales:	Shi H, Yang X, Zhao H, Zhang S, Zu J, Zhang W, Shen X, Cui G, Hua F, Yan C
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/ae8dbb8bbe0b4b4cb6130c8319b71a46
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spelling	oai:doaj.org-article:ae8dbb8bbe0b4b4cb6130c8319b71a462021-12-02T00:35:43ZRanitidine reduced levodopa-induced dyskinesia by remodeling neurochemical changes in hemiparkinsonian model of rats1178-2021https://doaj.org/article/ae8dbb8bbe0b4b4cb6130c8319b71a462015-05-01T00:00:00Zhttp://www.dovepress.com/ranitidine-reduced-levodopa-induced-dyskinesia-by-remodeling-neurochem-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Hongjuan Shi,1,2,* Xinxin Yang,2,3,* Hui Zhao,4 Shenyang Zhang,2 Jie Zu,2 Wei Zhang,2 Xia Shen,2 Guiyun Cui,2,3 Fang Hua,2,3 Chuanzhu Yan1 1Department of Neurology, Qilu Hospital of Shangdong University, Jinan, 2Department of Neurology, Affiliated Hospital of Xuzhou Medical College, 3Institute of Neurological Diseases of Xuzhou Medical College, 4Department of Neurology, Xuzhou Central Hospital, Xuzhou, People’s Republic of China *These authors contributed equally to this work Background: Levodopa (L-dopa) remains the best drug in the treatment of Parkinson’s disease (PD). Unfortunately, long-term L-dopa caused motor complications, one of which is L-dopa-induced dyskinesia (LID). The precise mechanisms of LID are not fully understood. We have previously reported that ranitidine could reduce LID by inhibiting the activity of protein kinase A pathway in a rat model of PD. It is demonstrated that neurotransmitters such as γ-aminobutyric-acid (GABA) and glutamate (Glu) are also involved in the expression of LID. But whether ranitidine could reduce LID by remodeling the neurochemical changes is unknown. Methods: In the present study, we produced PD rats by injection of 6-hydroxydopamine. Then PD rats were treated with vehicle, L-dopa (6 mg/kg, plus benserazide 12 mg/kg, intraperitoneal [ip]) or L-dopa (6 mg/kg, plus benserazide 12 mg/kg, ip) plus ranitidine (10 mg/kg, oral). Abnormal voluntary movements were adopted to measure the antidyskinetic effect of ranitidine in PD rats. Rotarod tests were used to observe whether ranitidine treatment affects the antiparkinsonian effect of L-dopa. In vivo microdialysis was used to measure nigral GABA and striatal Glu in PD rats. Results: We found that ranitidine pretreatment reduced abnormal voluntary movements in L-dopa-primed PD rats without affecting the antiparkinsonian effect of L-dopa. In parallel with behavioral improvement, ranitidine pretreatment reduced protein kinase A activity and suppressed the surge of nigral GABA and striatal Glu. Conclusion: These data indicated that ranitidine could reduce LID by modeling neurochemical changes induced by L-dopa, suggesting a novel mechanism of ranitidine in the treatment of LID. Keywords: ranitidine, Parkinson’s disease, levodopa-induced dyskinesia, PKA, γ-aminobutyric-acid, glutamateShi HYang XZhao HZhang SZu JZhang WShen XCui GHua FYan CDove Medical PressarticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol 2015, Iss default, Pp 1331-1337 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Shi H Yang X Zhao H Zhang S Zu J Zhang W Shen X Cui G Hua F Yan C Ranitidine reduced levodopa-induced dyskinesia by remodeling neurochemical changes in hemiparkinsonian model of rats
description	Hongjuan Shi,1,2,* Xinxin Yang,2,3,* Hui Zhao,4 Shenyang Zhang,2 Jie Zu,2 Wei Zhang,2 Xia Shen,2 Guiyun Cui,2,3 Fang Hua,2,3 Chuanzhu Yan1 1Department of Neurology, Qilu Hospital of Shangdong University, Jinan, 2Department of Neurology, Affiliated Hospital of Xuzhou Medical College, 3Institute of Neurological Diseases of Xuzhou Medical College, 4Department of Neurology, Xuzhou Central Hospital, Xuzhou, People’s Republic of China *These authors contributed equally to this work Background: Levodopa (L-dopa) remains the best drug in the treatment of Parkinson’s disease (PD). Unfortunately, long-term L-dopa caused motor complications, one of which is L-dopa-induced dyskinesia (LID). The precise mechanisms of LID are not fully understood. We have previously reported that ranitidine could reduce LID by inhibiting the activity of protein kinase A pathway in a rat model of PD. It is demonstrated that neurotransmitters such as γ-aminobutyric-acid (GABA) and glutamate (Glu) are also involved in the expression of LID. But whether ranitidine could reduce LID by remodeling the neurochemical changes is unknown. Methods: In the present study, we produced PD rats by injection of 6-hydroxydopamine. Then PD rats were treated with vehicle, L-dopa (6 mg/kg, plus benserazide 12 mg/kg, intraperitoneal [ip]) or L-dopa (6 mg/kg, plus benserazide 12 mg/kg, ip) plus ranitidine (10 mg/kg, oral). Abnormal voluntary movements were adopted to measure the antidyskinetic effect of ranitidine in PD rats. Rotarod tests were used to observe whether ranitidine treatment affects the antiparkinsonian effect of L-dopa. In vivo microdialysis was used to measure nigral GABA and striatal Glu in PD rats. Results: We found that ranitidine pretreatment reduced abnormal voluntary movements in L-dopa-primed PD rats without affecting the antiparkinsonian effect of L-dopa. In parallel with behavioral improvement, ranitidine pretreatment reduced protein kinase A activity and suppressed the surge of nigral GABA and striatal Glu. Conclusion: These data indicated that ranitidine could reduce LID by modeling neurochemical changes induced by L-dopa, suggesting a novel mechanism of ranitidine in the treatment of LID. Keywords: ranitidine, Parkinson’s disease, levodopa-induced dyskinesia, PKA, γ-aminobutyric-acid, glutamate
format	article
author	Shi H Yang X Zhao H Zhang S Zu J Zhang W Shen X Cui G Hua F Yan C
author_facet	Shi H Yang X Zhao H Zhang S Zu J Zhang W Shen X Cui G Hua F Yan C
author_sort	Shi H
title	Ranitidine reduced levodopa-induced dyskinesia by remodeling neurochemical changes in hemiparkinsonian model of rats
title_short	Ranitidine reduced levodopa-induced dyskinesia by remodeling neurochemical changes in hemiparkinsonian model of rats
title_full	Ranitidine reduced levodopa-induced dyskinesia by remodeling neurochemical changes in hemiparkinsonian model of rats
title_fullStr	Ranitidine reduced levodopa-induced dyskinesia by remodeling neurochemical changes in hemiparkinsonian model of rats
title_full_unstemmed	Ranitidine reduced levodopa-induced dyskinesia by remodeling neurochemical changes in hemiparkinsonian model of rats
title_sort	ranitidine reduced levodopa-induced dyskinesia by remodeling neurochemical changes in hemiparkinsonian model of rats
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/ae8dbb8bbe0b4b4cb6130c8319b71a46
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Ranitidine reduced levodopa-induced dyskinesia by remodeling neurochemical changes in hemiparkinsonian model of rats

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