{"doi":"10.1111/bph.16370","title":"Transient receptor potential ankyrin 1 channel modulates the abuse‐related mechanisms of methamphetamine through interaction with dopamine transporter","abstract":"BACKGROUND AND PURPOSE: Methamphetamine (METH) use disorder has risen dramatically over the past decade, and there are currently no FDA-approved medications due, in part, to gaps in our understanding of the pharmacological mechanisms related to METH action in the brain. EXPERIMENTAL APPROACH: Here, we investigated whether transient receptor potential ankyrin 1 (TRPA1) mediates each of several METH abuse-related behaviours in rodents: self-administration, drug-primed reinstatement, acquisition of conditioned place preference, and hyperlocomotion. Additionally, METH-induced molecular (i.e., neurotransmitter and protein) changes in the brain were compared between wild-type and TRPA1 knock-out mice. Finally, the relationship between TRPA1 and the dopamine transporter was investigated through immunoprecipitation and dopamine reuptake assays. KEY RESULTS: TRPA1 antagonism blunted METH self-administration and drug-primed reinstatement of METH-seeking behaviour. Further, development of METH-induced conditioned place preference and hyperlocomotion were inhibited by TRPA1 antagonist treatment, effects that were not observed in TRPA1 knock-out mice. Similarly, molecular studies revealed METH-induced increases in dopamine levels and expression of dopamine system-related proteins in wild-type, but not in TRPA1 knock-out mice. Furthermore, pharmacological blockade of TRPA1 receptors reduced the interaction between TRPA1 and the dopamine transporter, thereby increasing dopamine reuptake activity by the transporter. CONCLUSION AND IMPLICATIONS: This study demonstrates that TRPA1 is involved in the abuse-related behavioural effects of METH, potentially through its modulatory role in METH-induced activation of dopaminergic neurotransmission. Taken together, these data suggest that TRPA1 may be a novel therapeutic target for treating METH use disorder.","journal":"British Journal of Pharmacology","year":2024,"id":465351,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9501,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1296764,"name":"Youyoung Lee","orcid":null,"position":1,"is_corresponding":false},{"id":1296404,"name":"Audrey Lynn Donio","orcid":"0000-0002-7404-1791","position":2,"is_corresponding":false},{"id":1296765,"name":"Seon‐Kyung Kim","orcid":null,"position":3,"is_corresponding":false},{"id":1296766,"name":"Bo‐Ram Lee","orcid":null,"position":4,"is_corresponding":false},{"id":1296767,"name":"Jee‐Yeon Seo","orcid":null,"position":5,"is_corresponding":false},{"id":1296768,"name":"Dooti Kundu","orcid":null,"position":6,"is_corresponding":false},{"id":1296405,"name":"Kyeong‐Man Kim","orcid":"0000-0002-8138-4135","position":7,"is_corresponding":false},{"id":428266,"name":"Stephen J. Kohut","orcid":"0000-0002-6906-8818","position":8,"is_corresponding":false},{"id":1296406,"name":"Seok‐Yong Lee","orcid":"0000-0003-4162-1981","position":9,"is_corresponding":false},{"id":1296407,"name":"Choon‐Gon Jang","orcid":"0000-0002-2266-0566","position":10,"is_corresponding":false},{"id":1279245,"name":"Kwang‐Hyun Hur","orcid":"0000-0003-3654-4002","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T02:04:46.201722Z","pmid":"38644533","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":[]}