{"doi":"10.3390/cells12060837","title":"Broad Serotonergic Actions of Vortioxetine as a Promising Avenue for the Treatment of L-DOPA-Induced Dyskinesia","abstract":"Parkinson’s Disease (PD) is a neurodegenerative disorder characterized by motor symptoms that result from loss of nigrostriatal dopamine (DA) cells. While L-DOPA provides symptom alleviation, its chronic use often results in the development of L-DOPA-induced dyskinesia (LID). Evidence suggests that neuroplasticity within the serotonin (5-HT) system contributes to LID onset, persistence, and severity. This has been supported by research showing 5-HT compounds targeting 5-HT1A/1B receptors and/or the 5-HT transporter (SERT) can reduce LID. Recently, vortioxetine, a multimodal 5-HT compound developed for depression, demonstrated acute anti-dyskinetic effects. However, the durability and underlying pharmacology of vortioxetine’s anti-dyskinetic actions have yet to be delineated. To address these gaps, we used hemiparkinsonian rats in Experiment 1, examining the effects of sub-chronic vortioxetine on established LID and motor performance. In Experiment 2, we applied the 5-HT1A antagonist WAY-100635 or 5-HT1B antagonist SB-224289 in conjunction with L-DOPA and vortioxetine to determine the contributions of each receptor to vortioxetine’s effects. The results revealed that vortioxetine consistently and dose-dependently attenuated LID while independently, 5-HT1A and 5-HT1B receptors each partially reversed vortioxetine’s effects. Such findings further support the promise of pharmacological strategies, such as vortioxetine, and indicate that broad 5-HT actions may provide durable responses without significant side effects.","journal":"Cells","year":2023,"id":358274,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1108735,"name":"Kayla K. Elder","orcid":null,"position":1,"is_corresponding":false},{"id":774668,"name":"Michael Coyle","orcid":"0000-0002-0575-7729","position":2,"is_corresponding":false},{"id":1108390,"name":"Ashley Centner","orcid":"0000-0002-9997-1602","position":3,"is_corresponding":false},{"id":1108736,"name":"Natalie Lipari","orcid":null,"position":4,"is_corresponding":false},{"id":1108391,"name":"Sophie R. Cohen","orcid":"0000-0002-3758-5917","position":5,"is_corresponding":false},{"id":1108392,"name":"John Glinski","orcid":"0000-0003-4339-433X","position":6,"is_corresponding":false},{"id":1108737,"name":"N’Senga Kinzonzi","orcid":null,"position":7,"is_corresponding":false},{"id":1108738,"name":"Emily Wheelis","orcid":null,"position":8,"is_corresponding":false},{"id":1108739,"name":"Grace McManus","orcid":null,"position":9,"is_corresponding":false},{"id":495697,"name":"Fredric P. Manfredsson","orcid":"0000-0001-5802-5487","position":10,"is_corresponding":false},{"id":742512,"name":"Christopher Bishop","orcid":"0000-0003-4623-1085","position":11,"is_corresponding":false},{"id":1108389,"name":"Carla Budrow","orcid":"0000-0002-6339-7741","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T01:13:43.629667Z","pmid":"36980178","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}