Effects Of Levodopa On Number Of Cells Expressing D2 Receptor In Hemiparkinsonian Rat Model

Objective To establish hemiparkinsonian rat model and investigate theeffect of L-dopa on number of cells expressing D2 receptor and itsmechanism in the hemiparkinsonian rat model. MethodHealthy 64 male Sprague-Dawley rats weighting 180 to 250 g, divided into 4 groups : model group, 6-OHDA 8 g(4 1) was injected stereotaxically to right side of the mesencephic ventral tegmental area(VTA) and substantia nigra pars compact(SNc) in 46 rats; control group, 4 1 saline was injected stereotaxically to the same area in 6 rats; sham group, 6 rats without injective needle inserted into the brain; normal group, 6 normal rats. Two weeks after operation, rats of model, control, and sham groups were tested for apomorphine(0.5mg/kg,ip)-inducedcircling behavior. If rat rotated to the left side, cumulative rotations were recorded within 30 minutes post-injection. It is successful parkinsonianmodel, if rotations per minute exceed 7. Successful PD model rats were selected and divided into three groups with each group of 6 rats: 6-OHDA group, sacrificed after the set of model and rat brains were sliced and stored in -20 refrigerator; 6-OHDA+L-DOPA group, injection of L-dopa (100mg/kg/d,ip) for 15 days; 6-OHDA+Saline group, injection of saline (Iml/d, ip) for 15 days. After treatment in the 6-OHDA+L-DOPA Group and 6-OHDA+Saline Group, the rats were killed and the brains were sliced. The expression of tyroside hydroxylase(TH) in substantia nigra and D2 receptor in striatum of rats from all groups were detected by immunohistochemical staining. ResultThere were 25 rats having circling behavior to left receiving apomorphine 2 weeks after operatin, rotations cumulated within 30 minutes exceeded 210. The number of cells expressing TH in substantia nigra of lesioned side in 6-OHDA group decreased significantly compared with that of normal group, ipsilateral control group and sham group(p<0.001). We found the number of cells expressing D2 receptors in striatum of lesioned side increased significantly compared with that of normal group, ipsilateral striatum of control group and the shame group (p<0.01). The number of cells expressing D2 receptors in striatum of lesioned side in control group and sham group had no difference compared with that of normal group(p>0.01). Percentage of difference in D2 receptor between lesioned side and intact side was significantly correlated with rotations cumulated within 30 minutes(r=0.927,p<0.01). After administration of levodopa for 15 days, we found the number of cells expressing D2 receptor of striatum decreased significantly in lesioned side of 6-OHDA+L-DOPA group compared with that of 6-OHDA group and 6-OHDA+Saline group (p<0.01). No significant difference was found in the number of cells expressing D2 receptor in striatum of lesioned side between 6-OHDA group and 6-OHDA+Saline group (p>0.01).ConclusionDopaminergic neurons in substantia nigra pars compact of lesioned side died greatly in the hemiparkinsonian model, survival neurons is only 13.90% of that of intact side. It can mimic change of pathology in PD. Dopaminergic D2 receptor of striatum in lesioned side was up-regulated in PD rats model, percentage of difference in D2 receptor between lesioned side and intact side was correlated with rotations cumulated within 30 minutes, Levodopa can induce down-regulation of Dopamine D2 receptors in the striatum of parkinsonian rat model.