{"doi":"10.1111/bph.15244","title":"(±)VK4‐40, a novel dopamine D<sub>3</sub> receptor partial agonist, attenuates cocaine reward and relapse in rodents","abstract":"Background and Purpose Despite widespread abuse of cocaine, there are no approved treatments for cocaine use disorder. Chronic cocaine use is associated with up‐regulated dopamine D 3 receptor expression in the brain. Therefore, most D 3 ‐based medication development has focused on D 3 antagonists. However, D 3 antagonists do not attenuate cocaine intake under “easy” self‐administration conditions, when response requirements are low. We evaluated a novel, highly selective and metabolically stable D 3 partial agonist, (±)VK4‐40, for its efficacy in reducing cocaine intake and relapse to drug seeking. Experimental Approach The impact of (±)VK4‐40 on cocaine intake and relapse was evaluated using intravenous self‐administration procedures under a fixed‐ratio 2 reinforcement schedule and cocaine‐primed reinstatement conditions in rats. Optogenetic brain‐stimulation reward procedures were used to evaluate the interaction of (±)VK4‐40 and cocaine in the mesolimbic dopamine system in mice. Sucrose self‐administration in rats and a conditioned place preference paradigm in mice were used to evaluate the abuse potential of (±)VK4‐40 alone and other unwanted effects. Key Results (±)VK4‐40 dose‐dependently reduced cocaine self‐administration and cocaine‐primed reinstatement of drug‐seeking behaviour. (±)VK4‐40 also inhibited cocaine‐enhanced brain‐stimulation reward caused by optogenetic stimulation of dopamine neurons in the ventral tegmental area. (±)VK4‐40 alone decreased brain‐stimulation reward but produced neither conditioned place preference nor place aversion. This new D 3 partial agonist also failed to alter oral sucrose self‐administration. Conclusion and Implications The novel D 3 partial agonist, (±)VK4‐40 attenuates cocaine reward and relapse in rodents, without significant unwanted effects. These findings support further investigation of D 3 partial agonists as putative treatments for cocaine use disorder.","journal":"British Journal of Pharmacology","year":2020,"id":77511,"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":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9557,"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":282570,"name":"Yi He","orcid":"0000-0002-9503-0565","position":1,"is_corresponding":false},{"id":283712,"name":"Guo‐Hua Bi","orcid":null,"position":2,"is_corresponding":false},{"id":405567,"name":"Zhi‐Bing You","orcid":null,"position":3,"is_corresponding":false},{"id":405568,"name":"Jianjing Cao","orcid":null,"position":4,"is_corresponding":false},{"id":282571,"name":"Zheng‐Xiong Xi","orcid":"0000-0001-6482-8104","position":5,"is_corresponding":false},{"id":348848,"name":"Amy Hauck Newman","orcid":"0000-0001-9065-4072","position":6,"is_corresponding":false},{"id":282569,"name":"Chloe J. Jordan","orcid":"0000-0002-1843-227X","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-18T21:49:16.197289Z","pmid":"32851643","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":[]}