{"doi":"10.1111/adb.13165","title":"Metformin in nucleus accumbens core reduces cue‐induced cocaine seeking in male and female rats","abstract":"This study investigated the potential therapeutic effects of the FDA-approved drug metformin on cue-induced reinstatement of cocaine seeking. Metformin (dimethyl-biguanide) is a first-line treatment for type II diabetes that, among other mechanisms, is involved in the activation of adenosine monophosphate activated protein kinase (AMPK). Cocaine self-administration and extinction is associated with decreased levels of phosphorylated AMPK within the nucleus accumbens core (NAcore). Previously, it was shown that increasing AMPK activity in the NAcore decreased cue-induced reinstatement of cocaine seeking. Decreasing AMPK activity produced the opposite effect. The goal of the present study was to determine if metformin in the NAcore reduces cue-induced cocaine seeking in adult male and female Sprague Dawley rats. Rats were trained to self-administer cocaine followed by extinction prior to cue-induced reinstatement trials. Metformin microinjected in the NAcore attenuated cue-induced reinstatement in male and female rats. Importantly, metformin's effects on cocaine seeking were not due to a general depression of spontaneous locomotor activity. In female rats, metformin's effects did generalize to a reduction in cue-induced reinstatement of sucrose seeking. These data support a potential role for metformin as a pharmacotherapy for cocaine use disorder but warrant caution given the potential for metformin's effects to generalize to a natural reward in female rats.","journal":"Addiction Biology","year":2022,"id":273905,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9589,"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":818522,"name":"Alexis Willard","orcid":null,"position":1,"is_corresponding":false},{"id":372217,"name":"Sarah Mulloy","orcid":"0000-0001-6651-4344","position":2,"is_corresponding":false},{"id":818523,"name":"Noor Ibrahim","orcid":null,"position":3,"is_corresponding":false},{"id":818524,"name":"Allegra Sciaccotta","orcid":null,"position":4,"is_corresponding":false},{"id":818525,"name":"Mark Schonfeld","orcid":null,"position":5,"is_corresponding":false},{"id":497585,"name":"Sade Spencer","orcid":"0000-0001-8663-9056","position":6,"is_corresponding":false},{"id":712698,"name":"Amy E. Chan","orcid":"0000-0002-7362-4936","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T00:28:07.776043Z","pmid":"35470560","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":[]}