{"doi":"10.3389/fnins.2020.00785","title":"PT320, Sustained-Release Exendin-4, Mitigates L-DOPA-Induced Dyskinesia in a Rat 6-Hydroxydopamine Model of Parkinson’s Disease","abstract":"BACKGROUND: We previously demonstrated that subcutaneous administration of PT320, a sustained-release (SR) form of exendin-4, resulted in the long-term maintenance of steady-state exenatide (exendin-4) plasma and target levels in 6-hydroxydopamine (6-OHDA)-pretreated animals. Additionally, pre- or post-treatment with PT320 mitigated the early stage of 6-OHDA-induced dopaminergic neurodegeneration. The purpose of this study was to evaluate the effect of PT320 on L-3,4-dihydroxyphenylalanine (L-DOPA)-induced abnormal involuntary movements (AIMs) in the rat 6-OHDA model of Parkinson's disease. METHODS: Adult male Sprague-Dawley rats were unilaterally lesioned in the right medial forebrain bundle by 6-OHDA. L-DOPA and benserazide were given daily for 22 days, starting from 4 weeks after lesioning. PT320 was co-administered weekly for 3 weeks. AIM was evaluated on days 1, 16, and 22 after initiating L-DOPA/benserazide + PT320 treatment. Brain tissues were subsequently collected for HPLC measurements of dopamine (DA) and metabolite concentrations. RESULTS: L-DOPA/benserazide increased AIMs of limbs and axial as well as the sum of all dyskinesia scores (ALO) over 3 weeks. PT320 significantly reduced the AIM scores of limbs, orolingual, and ALO. Although PT320 did not alter DA levels in the lesioned striatum, PT320 significantly attenuated 6-OHDA-enhanced DA turnover. CONCLUSION: PT320 attenuates L-DOPA/benserazide-induced dyskinesia in a 6-OHDA rat model of PD and warrants clinical evaluation to mitigate Parkinson's disease in humans.","journal":"Frontiers in Neuroscience","year":2020,"id":78140,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9533,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":406770,"name":"Shuchun Chen","orcid":"0000-0002-7747-3901","position":1,"is_corresponding":false},{"id":408049,"name":"Yung-Yung Yang","orcid":null,"position":2,"is_corresponding":false},{"id":319983,"name":"Elliot J. Glotfelty","orcid":"0000-0001-5125-8720","position":3,"is_corresponding":false},{"id":408050,"name":"Jin Ho Jung","orcid":null,"position":4,"is_corresponding":false},{"id":406771,"name":"Hee-Kyung Kim","orcid":"0000-0003-2103-4835","position":5,"is_corresponding":false},{"id":408051,"name":"Ho-Il Choi","orcid":null,"position":6,"is_corresponding":false},{"id":307620,"name":"Doo‐Sup Choi","orcid":"0000-0002-6796-9938","position":7,"is_corresponding":false},{"id":333743,"name":"Barry J. Hoffer","orcid":"0000-0002-1122-9025","position":8,"is_corresponding":false},{"id":297917,"name":"Nigel H. Greig","orcid":"0000-0002-3032-1468","position":9,"is_corresponding":false},{"id":406772,"name":"Yun Wang","orcid":"0000-0001-7983-5905","position":10,"is_corresponding":false},{"id":406769,"name":"Seong‐Jin Yu","orcid":"0000-0001-7500-5883","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-18T21:49:40.769098Z","pmid":"32848559","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":[]}