## 4 Discussion  
Here we established a LID rat model using the well-recognized intraperitoneal injection of L-DOPA and benserazide after unilateral 6-OHDA lesioning of the nigrostriatal pathway. Because a subset of SD rats is LID resistant [30; 31], we divided rats in our study into the LID and NLID groups according to whether the model was successful. High-throughput sequencing was then used to screen the DEcircRNAs in the striatum. Using bioinformatics approaches, we further narrowed the scope to focus on a subset of circRNAs that may have played a key regulatory role and found mo-Rsf1_0012 may be related to the occurrence and development of LID. This possibility was further verified by PCR results. According to the mechanism of ceRNA, we speculated that mo-Rsf1_0012 might function as miRNA sponges to abrogate the inhibitory impact of mo-miR-298-5p on target genes. The dual-luciferase reporter genes experiment confirmed this idea. Although no animal model can fully replicate human PD, the unilateral striatum of SD rats damaged by 6-OHDA is one of the most well-studied PD models. The substantia nigra dopaminergic neuron degeneration and loss, glial cell proliferation, substantia nigra and striatum TH activity, and dopamine decrease are similar to that of human PD. Apomorphine-induced rotation behavior can be used to quantify PD behavior and facilitate evaluation by researchers. However, it must be noted that this model belongs to an acute injury model and cannot simulate the characteristics of the chronic progressive course of PD in humans. Human LID can be divided into different subtypes with different clinical manifestations and mechanisms, including peak-dose dyskinesia, diphasic dyskinesia, and \"off\" dystonia [32]. The widely used LID rat model adopted in this study can simulate the peak-dose dyskinesia well [33; 34]. A certain percentage of SD rats showed resistance to L-DOPA during the preparation of the LID rat model [35]. Therefore, studying the differences between LID susceptible and LID resistant SD rats may be important in clarifying the molecular mechanism of LID. Starting from this phenomenon, [PERSON] et al. characterized the key regulatory role of Nurr1 in LID [36]. In the present study, the incidence and severity of AIMs in rats increased with an increase in levodopa dose, which was consistent with the phenomenon reported in LID patients [37]. The details of LID pathogenic mechanisms are not completely understood, similar to PD mechanisms. According to the classic neural circuit model, contrary to the formation of PD, after long-term administration of levodopa, the direct pathway is hyperactive, and the indirect pathway is inhibited. However, this general model cannot explain all the clinical phenomena and experimental results of LID. LID is associated with molecular changes mediated by dopamine D1 receptors in the striatum, including phosphorylation of ERK, MSK1, and histone H3 at the level of the medium spiny neuron of the striatal nigral pathway [26]. Activation of D1/DARP32 by levodopa induces the translocation of  
Figure 5: Dual-luciferase reporter assay and target genes expression. (**A**) Wild-type (WT) and mutated-type (MT) sequences of the putative binding sites between mo-Rsf1_0012 and mo-miR-298-5p. (**B**) Dual-luciferase reporter assays were performed to validate the association of mo-Rsf1_0012 and mo-miR-298-5p. Compared with the NC mimics, mo-miR-298-5p significantly reduced the luciferase activity of the WT reporter, while mo-miR-298-5p did not affect the luciferase activity of the MT reporter. (**C**) PCP4 and TBP in LID group were significantly increased in LID group (\(n=6\)) compared with NLID group (\(n=6\)). \({}^{*}p<0.05\), \({}^{***}p<0.001\). phosphorylated ERK in the nucleus and subsequent activation of MSK1, which plays a key role in regulating synaptic plasticity and transcriptional activity [38]. Functional analysis showed that many host genes of DEcircRNAs such as N4 bp1, Ubr5, Klh2, Rc3h2, Ankib1, Ccnc, Birc6, Trip12, Cdc23, and Kdm2a were involved in ubiquitination.