{"doi":"10.1177/0269881120959611","title":"Effect of serotonin transporter genotype on carbon dioxide-induced fear-related behavior in mice","abstract":"Background: Inhaling 35% carbon dioxide induces an emotional and symptomatic state in humans closely resembling naturally occurring panic attacks, the core symptom of panic disorder. Previous research has suggested a role of the serotonin system in the individual sensitivity to carbon dioxide. In line with this, we previously showed that a variant in the SLC6A4 gene, encoding the serotonin transporter, moderates the fear response to carbon dioxide in humans. To study the etiological basis of carbon dioxide-reactivity and panic attacks in more detail, we recently established a translational mouse model. Aim: The purpose of this study was to investigate whether decreased expression of the serotonin transporter affects the sensitivity to carbon dioxide. Methods: Based on our previous work, wildtype and serotonin transporter deficient (+/–, –/–) mice were monitored while being exposed to carbon dioxide-enriched air. In wildtype and serotonin transporter +/– mice, also cardio-respiration was assessed. Results: For most behavioral measures under air exposure, wildtype and serotonin transporter +/– mice did not differ, while serotonin transporter –/– mice showed more fear-related behavior. Carbon dioxide exposure evoked a marked increase in fear-related behaviors, independent of genotype, with the exception of time serotonin transporter –/– mice spent in the center zone of the modified open field test and freezing in the two-chamber test. On the physiological level, when inhaling carbon dioxide, the respiratory system was strongly activated and heart rate decreased independent of genotype. Conclusion: Carbon dioxide is a robust fear-inducing stimulus. It evokes inhibitory behavioral responses such as decreased exploration and is associated with a clear respiratory profile independent of serotonin transporter genotype.","journal":"Journal of Psychopharmacology","year":2020,"id":114325,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9484,"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":284884,"name":"Daniël van den Hove","orcid":"0000-0003-4047-3198","position":1,"is_corresponding":false},{"id":537858,"name":"Magdalena T. Weidner","orcid":"0000-0002-6195-8912","position":2,"is_corresponding":false},{"id":537859,"name":"Gordon F. Buchanan","orcid":"0000-0003-2371-4455","position":3,"is_corresponding":false},{"id":322903,"name":"Harry W.M. Steinbusch","orcid":"0000-0002-7667-0604","position":4,"is_corresponding":false},{"id":273443,"name":"Klaus‐Peter Lesch","orcid":"0000-0001-8348-153X","position":5,"is_corresponding":false},{"id":19443,"name":"Koen Schruers","orcid":"0000-0003-0134-406X","position":6,"is_corresponding":false},{"id":537857,"name":"Nicole Leibold","orcid":"0000-0003-2347-5423","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-18T23:13:29.674622Z","pmid":"33103571","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":[]}