{"doi":"10.1101/2023.10.27.564447","title":"Arrestin-3-assisted activation of JNK3 mediates dopaminergic behavioral and signaling plasticity in vivo","abstract":"In rodents with unilateral ablation of the substantia nigra neurons supplying dopamine to the striatum, chronic treatment with the dopamine precursor L-DOPA or dopamine agonists induces a progressive increase of behavioral responses, a process known as behavioral sensitization. The sensitization is blunted in arrestin-3 knockout mice. Using virus-mediated gene delivery to the dopamine-depleted striatum of arrestin-3 knockout mice, we found that the restoration of arrestin-3 fully rescued behavioral sensitization, whereas its mutant defective in JNK activation did not. A 25-residue arrestin-3-derived peptide that facilitates JNK3 activation in cells, expressed ubiquitously or selectively in the direct pathway striatal neurons, fully rescued sensitization, whereas an inactive homologous arrestin-2-derived peptide did not. Behavioral rescue was accompanied by the restoration of JNK3 activity and of JNK-dependent phosphorylation of the transcription factor c-Jun in the dopamine-depleted striatum. Thus, arrestin-3-dependent JNK3 activation in direct pathway neurons is a critical element of the molecular mechanism underlying sensitization.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":413369,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"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":395410,"name":"Chen Zheng","orcid":"0000-0002-3610-5715","position":1,"is_corresponding":false},{"id":411575,"name":"Jeffery L. Dunning","orcid":"0000-0003-0397-4006","position":2,"is_corresponding":false},{"id":1194755,"name":"Mohamed S. Ahmed","orcid":"0000-0001-9249-6231","position":3,"is_corresponding":false},{"id":1043825,"name":"Connie Ge","orcid":null,"position":4,"is_corresponding":false},{"id":1194756,"name":"F. Sanders Pair","orcid":"0000-0003-0019-0740","position":5,"is_corresponding":false},{"id":271822,"name":"Vsevolod V. Gurevich","orcid":"0000-0002-3950-5351","position":6,"is_corresponding":false},{"id":271823,"name":"Eugenia V. Gurevich","orcid":"0000-0002-0563-8295","position":7,"is_corresponding":false},{"id":477691,"name":"M. Rafiuddin Ahmed","orcid":"0000-0002-2643-0813","position":0,"is_corresponding":true}],"reference_count":83,"raw_metadata":null,"created_at":"2026-07-19T01:21:57.641539Z","pmid":"37961199","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":[]}