{"doi":"10.1101/2023.06.08.544242","title":"Punishment resistance for cocaine is associated with inflexible habits in rats","abstract":"Addiction is characterized by continued drug use despite negative consequences. In an animal model, a subset of rats continues to self-administer cocaine despite footshock consequences, showing punishment resistance. We sought to test the hypothesis that punishment resistance arises from failure to exert goal-directed control over habitual cocaine seeking. While habits are not inherently permanent or maladaptive, continued use of habits under conditions that should encourage goal-directed control makes them maladaptive and inflexible. We trained male and female Sprague Dawley rats on a seeking-taking chained schedule of cocaine self-administration (2 h/day). We then exposed them to 4 days of punishment testing, in which footshock (0.4 mA, 0.3 s) was delivered randomly on one-third of trials, immediately following completion of seeking and prior to extension of the taking lever. Before and after punishment testing (4 days pre-punishment and ≥4 days post-punishment), we assessed whether cocaine seeking was goal-directed or habitual using outcome devaluation via cocaine satiety. We found that punishment resistance was associated with continued use of habits, whereas punishment sensitivity was associated with increased goal-directed control. Although punishment resistance was not predicted by habitual responding pre-punishment, it was associated with habitual responding post-punishment. In parallel studies of food self-administration, we similarly observed that punishment resistance was associated with habitual responding post-punishment but not pre-punishment. These findings indicate that punishment resistance is related to habits that have become inflexible and persist under conditions that should encourage a transition to goal-directed behavior.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":396653,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9515,"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":1172424,"name":"Morgan S. Paladino","orcid":null,"position":1,"is_corresponding":false},{"id":418200,"name":"Adelis M. Cruz","orcid":"0000-0001-8564-6684","position":2,"is_corresponding":false},{"id":418201,"name":"Haley F. Spencer","orcid":"0000-0001-8838-1909","position":3,"is_corresponding":false},{"id":1172425,"name":"Payton L. Kahanek","orcid":null,"position":4,"is_corresponding":false},{"id":1172426,"name":"Lauren N. Scarborough","orcid":null,"position":5,"is_corresponding":false},{"id":1172427,"name":"Sandra F. Georges","orcid":null,"position":6,"is_corresponding":false},{"id":418203,"name":"Rachel J. Smith","orcid":"0000-0002-5212-561X","position":7,"is_corresponding":false},{"id":985726,"name":"Bradley O. Jones","orcid":"0000-0002-5213-3759","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-07-19T01:19:31.472087Z","pmid":"37333299","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":[]}