Effect of Zishenpingchan Granule on Neurobehavioral Manifestations and the Activity and Gene Expression of Striatal Dopamine D1 Receptors of Rats with Levodopa-Induced Dyskinesias

Abstract

Objective: To observe the effects of Traditional Chinese Medicine on neurobehavioral manifestations and the activity and mRNA expression of striatal dopamine D1 receptors of rats with levodopa-induced dyskinesias (LID). Methods: The rat model of Parkinson's disease (PD) was established by 6-OHDA; then, the model of LID in rat was produced by injecting levodopa (LD) and benserazide for 4 weeks. The rats were divided into normal control group, LID model group and TCM intervention group. After 4 weeks of treatment, the effect of TCM on abnormal involuntary movement (AIM) score of rats with LID, peak dose rotation and efficacy time of levodopa (LD) were observed. The maximum binding capacity (Bmax) and equilibrium dissociation constant (KD) of striatal dopamine D1 receptors of rats were determined. The mRNA expression of dopamine D1 receptors was assayed by using real-time fluorescent quantitative PCR (FQ-PCR). Result: With the extension of LD treatment time, the AIM score and peak dose rotation of rats in the LID model group increased progressively. Comparing to the LD model group, TCM intervention could obviously reduce the AIM score and peak dose rotation of rats with LID (P < 0.05). The research of D1 receptor activity showed that level of Bmax increased (P < 0.01) and level of KD reduced (P < 0.01) in the LID model group and the TCM intervention group in comparison to those in the normal control group. The activity of D1 receptor increased obviously. TCM treatment could decrease the Bmax level, increase the KD level (P < 0.01) and lower the activity of D1 receptor. The results of FQ-PCR analysis revealed that the gene expression of D1 receptor was up-regulated in the LID model group (P < 0.01). TCM treatment can decrease over-expressed D1 receptor expression (P < 0.05). Conclusion: Over-activation in direct-pathway mediated by dopamine D1 receptor may be the main mechanism of LID. TCM effectively relieved LID symptoms through regulating the gene expression and activity of dopamine D1 receptors.