{"doi":"10.3389/fpsyt.2023.1122568","title":"Individual differences in the effects of midazolam on anxiety-like behavior, learning, reward, and choice behavior in male mice","abstract":"Introduction: The aim of the present study was to investigate the behavioral effects of the benzodiazepine midazolam in male mice, in models of anxiolysis, learning, and abuse-related effects. Methods: In a first set of experiments, male Swiss mice were submitted to the training session of a discriminative avoidance (DA) task on the elevated plus maze to evaluate anxiety-like behavior and learning after vehicle or midazolam (1, 2 or 5 mg/kg, i.g.) administration. The same animals were submitted to a conditioned place preference (CPP) protocol with midazolam (1, 2 or 5 mg/kg, i.g.). In a second experiment, outbred (Swiss) and inbred (C57BL/6) male mice were submitted to a two-bottle choice (TBC) oral midazolam drinking procedure. Animals were exposed to one sucrose bottle and one midazolam (0.008, 0.016 or 0.032 mg/ml) plus sucrose bottle. Results: the TBC procedure showed notable variability. A 2-step cluster analysis for the CPP data showed that midazolam data were well-fitted to 2 separate clusters (preference vs. aversion), albeit with the majority of mice showing preference (75%). Correlational and regression analyses showed no relationship between midazolam reward and anxiolytic-like effects (time spent in the open arms in the DA test) or learning/memory. Two-step cluster analysis of the TBC data also demonstrated that, regardless of strain, mice overall fell into two clusters identified as midazolam-preferring or midazolam-avoiding groups. Both midazolam preference and avoidance were concentration-dependent in a subset of mice. Discussion: Our findings show that midazolam preference is a multifactorial behavior, and is not dependent solely on the emergence of therapeutic (anxiolytic-like) effects, learning impairments, or on genetic factors (inbred vs. outbred animals).","journal":"Frontiers in Psychiatry","year":2023,"id":353655,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9609,"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":1100793,"name":"Meagan E. Follett","orcid":null,"position":1,"is_corresponding":false},{"id":1100794,"name":"Behaim Correia Dias-Júnior","orcid":null,"position":2,"is_corresponding":false},{"id":889412,"name":"Yasmim A. Serra","orcid":"0000-0003-2789-5011","position":3,"is_corresponding":false},{"id":889938,"name":"Natali D. Kisaki","orcid":null,"position":4,"is_corresponding":false},{"id":889413,"name":"Thaísa Barros-Santos","orcid":"0000-0002-5866-7954","position":5,"is_corresponding":false},{"id":889941,"name":"Nailton M. S. de Jesus","orcid":null,"position":6,"is_corresponding":false},{"id":1100795,"name":"Isa R. S. Rodrigues","orcid":null,"position":7,"is_corresponding":false},{"id":1100796,"name":"Larissa E. L. Macedo","orcid":null,"position":8,"is_corresponding":false},{"id":889418,"name":"Elena L. A. Malpezzi-Marinho","orcid":"0000-0002-8378-7069","position":9,"is_corresponding":false},{"id":889942,"name":"Alexandre J. Oliveira-Lima","orcid":null,"position":10,"is_corresponding":false},{"id":889419,"name":"E.A.V. Marinho","orcid":"0000-0002-3179-2819","position":11,"is_corresponding":false},{"id":454462,"name":"James K. Rowlett","orcid":"0000-0002-4077-5017","position":12,"is_corresponding":false},{"id":454461,"name":"Laís F. Berro","orcid":"0000-0003-4841-4117","position":13,"is_corresponding":false},{"id":889415,"name":"Caio Jovita-Farias","orcid":"0009-0001-5484-3025","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T01:13:02.680107Z","pmid":"36937711","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":[]}