Journal
NEUROPSYCHIATRIC DISEASE AND TREATMENT
Volume 11, Issue -, Pages 1331-1337Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/NDT.S80174
Keywords
ranitidine; Parkinson's disease; levodopa-induced dyskinesia; PKA; gamma-aminobutyric-acid; glutamate
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Funding
- National Natural Science Foundation of China [81301077, 81271344, 81271268]
- Natural Science Foundation of Jiangsu Higher Education Institutions [13KJB320026]
- Jiangsu Province Health Department [H200926]
- Jiangsu Specially-Appointed Professor Program
- social development of science and technology plan [XM13B058]
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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-dopainduced 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 gamma-aminobutyricacid (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.
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