{"doi":"10.1101/2023.05.18.541208","title":"K <sub>v</sub> 7 Channel Opener Retigabine Reduces Self-Administration of Cocaine but Not Sucrose in Rats","abstract":"ABSTRACT The increasing rates of drug misuse highlight the urgency of identifying improved therapeutics for treatment. Most drug-seeking behaviors that can be modeled in rodents utilize the repeated intravenous self-administration (SA) of drugs. Recent studies examining the mesolimbic pathway suggest that K v 7/KCNQ channels may contribute in the transition from recreational to chronic drug use. However, to date, all such studies used noncontingent, experimenter-delivered drug model systems, and the extent to which this effect generalizes to rats trained to self-administer drug is not known. Here, we tested the ability of retigabine (ezogabine), a K v 7 channel opener, to regulate instrumental behavior in male Sprague Dawley rats. We first validated the ability of retigabine to target experimenter-delivered cocaine in a CPP assay and found that retigabine reduced the acquisition of place preference. Next, we trained rats for cocaine-SA under a fixed-ratio or progressive-ratio reinforcement schedule and found that retigabine-pretreatment attenuated the self-administration of low to moderate doses of cocaine. This was not observed in parallel experiments, with rats self-administering sucrose, a natural reward. Compared to sucrose-SA, cocaine-SA was associated with reductions in the expression of the K v 7.5 subunit in the nucleus accumbens, without alterations in K v 7.2 and K v 7.3. Therefore, these studies reveal a reward specific reduction in SA behavior considered relevant for the study of long-term compulsive-like behavior and supports the notion that K v 7 is a potential therapeutic target for human psychiatric diseases with dysfunctional reward circuitry.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":407518,"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":0.9551,"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":1186459,"name":"Cody C. Diezel","orcid":"0000-0003-3144-7342","position":1,"is_corresponding":false},{"id":1186700,"name":"Mauricio Serna","orcid":null,"position":2,"is_corresponding":false},{"id":1186701,"name":"Grace Hala’ufia","orcid":null,"position":3,"is_corresponding":false},{"id":961195,"name":"Lisa Majuta","orcid":"0000-0002-7690-2356","position":4,"is_corresponding":false},{"id":582430,"name":"Kara R. Barber","orcid":"0000-0002-4042-9886","position":5,"is_corresponding":false},{"id":407436,"name":"Todd W. Vanderah","orcid":"0000-0003-0406-4354","position":6,"is_corresponding":false},{"id":961196,"name":"Arthur C. Riegel","orcid":"0000-0001-7758-4436","position":7,"is_corresponding":false},{"id":1186458,"name":"Esteban S. Urena","orcid":"0000-0003-1283-024X","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T01:21:10.867368Z","pmid":"37292619","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":[]}