{"doi":"10.1101/2022.07.26.501618","title":"Individual differences in oxycodone addiction-like behaviors in a large cohort of heterogeneous stock (HS) rats","abstract":"Abstract Family and twin studies demonstrate that genetic factors determine 20-60% of the vulnerability to opioid use disorder. However, the genes/alleles that mediate the risk of developing addiction-related behaviors, including the sensitivity to the analgesic efficacy of opioids, the development of tolerance, dependence, and escalation of oxycodone taking and seeking, have been ill-defined, thus hindering efforts to design pharmacological interventions to enable precision medicine strategies. Here we characterized oxycodone addiction-like behaviors in heterogeneous stock (HS) rats, that show high genetic diversity that mimics the high genetic variability in humans. HS rats were allowed to self-administer oxycodone for two h/daily for four days (ShA) and then moved to 12h/daily (LgA) for 14 days. Animals were screened for motivation to self-administer oxycodone using a progressive-ratio (PR) schedule of reinforcement and for the development of withdrawal-induced hyperalgesia and tolerance to the analgesic effects of oxycodone using the von-Frey and tail immersion tests, respectively. To reduce cohort-specific effects, we used cohorts of 46-60 rats and normalized the response level within cohorts using a Z-score. To take advantage of the four opioid-related behaviors and further identify subjects that are consistently vulnerable vs . resilient to compulsive oxycodone use, we computed an Addiction Index by averaging normalized responding (Z-scores) for the four behavioral tests. Results showed high individual variability between vulnerable and resilient rats, likely to facilitate the detection of gene variants associated with vulnerable vs . resilient individuals. Such data will have considerable translational value for designing follow-up studies in humans.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":298010,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":1,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9433,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":329614,"name":"Giordano de Guglielmo","orcid":"0000-0002-4782-7430","position":1,"is_corresponding":false},{"id":812995,"name":"Lieselot L. G. Carrette","orcid":"0000-0002-5217-2774","position":2,"is_corresponding":false},{"id":366160,"name":"Sierra Simpson","orcid":"0000-0002-1352-0617","position":3,"is_corresponding":false},{"id":722383,"name":"Jenni Kononoff","orcid":"0000-0001-6620-0679","position":4,"is_corresponding":false},{"id":366162,"name":"Adam Kimbrough","orcid":"0000-0001-9434-4987","position":5,"is_corresponding":false},{"id":409801,"name":"Lauren C. Smith","orcid":"0000-0002-4290-3262","position":6,"is_corresponding":false},{"id":366161,"name":"Kokila Shankar","orcid":"0000-0001-8269-8390","position":7,"is_corresponding":false},{"id":813001,"name":"Alicia Avelar","orcid":"0000-0003-1414-5748","position":8,"is_corresponding":false},{"id":811375,"name":"Dana Conlisk","orcid":"0000-0002-4641-7878","position":9,"is_corresponding":false},{"id":811374,"name":"Molly Brennan","orcid":"0000-0002-5443-1100","position":10,"is_corresponding":false},{"id":813687,"name":"Lani Tieu","orcid":null,"position":11,"is_corresponding":false},{"id":329616,"name":"Sharona Sedighim","orcid":"0009-0004-3865-3565","position":12,"is_corresponding":false},{"id":813686,"name":"Brent Boomhower","orcid":null,"position":13,"is_corresponding":false},{"id":811937,"name":"Lisa Maturin","orcid":null,"position":14,"is_corresponding":false},{"id":812996,"name":"McKenzie J. Fannon","orcid":"0000-0001-7473-7222","position":15,"is_corresponding":false},{"id":987038,"name":"Angelica Martinez","orcid":null,"position":16,"is_corresponding":false},{"id":813692,"name":"Caitlin Crook","orcid":null,"position":17,"is_corresponding":false},{"id":986590,"name":"Selen Dirik","orcid":"0009-0006-2429-4252","position":18,"is_corresponding":false},{"id":812997,"name":"Nathan Velarde","orcid":"0000-0002-2997-6504","position":19,"is_corresponding":false},{"id":813696,"name":"Paul Schweitzer","orcid":null,"position":20,"is_corresponding":false},{"id":813000,"name":"Sélène Bonnet-Zahedi","orcid":"0009-0008-8151-4850","position":21,"is_corresponding":false},{"id":813689,"name":"Dyar Othman","orcid":null,"position":22,"is_corresponding":false},{"id":987039,"name":"Benjamin Sichel","orcid":null,"position":23,"is_corresponding":false},{"id":987040,"name":"Kwynn Guess","orcid":null,"position":24,"is_corresponding":false},{"id":813002,"name":"Beverly Peng","orcid":"0009-0001-1511-3089","position":25,"is_corresponding":false},{"id":987041,"name":"Andrew S. Hu","orcid":null,"position":26,"is_corresponding":false},{"id":813693,"name":"Lucas Chun","orcid":null,"position":27,"is_corresponding":false},{"id":813695,"name":"Kristel K Milan","orcid":null,"position":28,"is_corresponding":false},{"id":812999,"name":"Justin Kai‐Chi Lau","orcid":"0000-0001-8327-0644","position":29,"is_corresponding":false},{"id":987042,"name":"Yicen Zheng","orcid":null,"position":30,"is_corresponding":false},{"id":813694,"name":"Ashley Vang","orcid":null,"position":31,"is_corresponding":false},{"id":551740,"name":"Leah C. Solberg Woods","orcid":"0000-0002-7943-798X","position":32,"is_corresponding":false},{"id":230002,"name":"Abraham A. Palmer","orcid":"0000-0003-3634-0747","position":33,"is_corresponding":false},{"id":329618,"name":"Olivier George","orcid":"0000-0002-3700-5003","position":34,"is_corresponding":false},{"id":329615,"name":"Marsida Kallupi","orcid":"0000-0002-8688-709X","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:31:31.270564Z","pmid":null,"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":[]}