title: Ranitidine reduced levodopa-induced dyskinesia by remodeling neurochemical changes in hemiparkinsonian model of rats.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, Qilu Hospital of Shangdong University, Jinan, People's Republic of China ; Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, People's Republic of China.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, People's Republic of China ; Institute of Neurological Diseases of Xuzhou Medical College, Xuzhou, People's Republic of China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Neurology, Xuzhou Central Hospital, Xuzhou, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, People's Republic of China.
authors.forename: Shenyang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zu
authors.affiliation: Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, People's Republic of China.
authors.forename: Xia
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, People's Republic of China ; Institute of Neurological Diseases of Xuzhou Medical College, Xuzhou, People's Republic of China.
authors.forename: Guiyun
authors.initials: G
authors.lastname: Cui
authors.affiliation: Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, People's Republic of China ; Institute of Neurological Diseases of Xuzhou Medical College, Xuzhou, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Hua
authors.affiliation: Department of Neurology, Qilu Hospital of Shangdong University, Jinan, People's Republic of China.
authors.forename: Chuanzhu
authors.initials: C
authors.lastname: Yan
keywords: PKA; Parkinson’s disease; glutamate; levodopa-induced dyskinesia; ranitidine; γ-aminobutyric-acid