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