Cortico-striatal gamma oscillations are modulated by dopamine D3 receptors in dyskinetic rats

Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Currently,studies have reported increased oscillation power in cases of levodopa-induced dyskinesia.However,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia.Furthermore,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is unclear.We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease.Furthermore,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma flow.Administration of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum flow.However,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum direction.These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.

Association between Tourette Syndrome and the Dopamine D3 Receptor Gene Rs6280

Background：Tourette syndrome （TS） is a complex,heterozygous genetic disorder.The number of molecular genetic studies have investigated several candidate genes,particularly those implicated in the dopamine system.The dopamine D3 receptor （DRD3） gene has been considered as a candidate gene in TS.There was not any report about the association study of TS and DRD3 gene in Han Chinese population.We combined a case-control genetic association analysis and nuclear pedigrees transmission disequilibrium test （TDT） analysis to investigate the association between DRD3 gene rs6280 single nucleotide polymorphisms （SNPs） and TS in a Han Chinese population.Methods：A total of 160 TS patients was diagnosed by the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition.The DRD3 gene rs6280 SNPs were genotyped by TaqMan SNP genotyping assay technique in all subjects.We used a case-control genetic association analysis to compare the difference in genotype and allele frequencies between 160 TS patients and 90 healthy controls.At the same time,we used TDT analysis to identify the DRD3 gene rs6280 transmission disequilibrium among 10l nuclear pedigrees.Results：The genotype and allele frequency of DRD3 gene rs6280 SNPs had no statistical difference between control group （90） and TS group （160） （χ^2 =3.647,P =0.161; χ^2 =0.643,P =0.423） using Chi-squared test.At the basis of the 101 nuclear pedigrees,TDT analysis showed no transmission disequilibrium ofDRD3 gene rs6280 SNPs （χ^2 =0; P =1）.Conclusions：Our findings provide no evidence for an association between DRD3 gene rs6280 and TS in the Han Chinese population.