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Despite promising early clinical trials, the mechanisms which underlie the effects of psychedelics are poorly understood. For example, key questions such as whether antidepressant and psychedelic effects involve related or independent mechanisms are unresolved. Preclinical studies in relevant animal models are key to understanding the pharmacology of psychedelics and translating these findings to explain efficacy and safety in patients. Understanding the mechanisms of action associated with the behavioural effects of psychedelic drugs can also support the identification of novel drug targets and more effective treatments. Here we review the behavioural approaches currently used to quantify the psychedelic and antidepressant effects of psychedelic drugs. We discuss conceptual and methodological issues, the importance of using clinically relevant doses and the need to consider possible sex differences in preclinical psychedelic studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LINKED ARTICLES<\/jats:title>\n                    <jats:p>\n                      This article is part of a themed issue Emerging Therapeutic Opportunities for Psychedelic and Related Drugs. To view the other articles in this section visit\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v183.14\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v183.14\/issuetoc<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.17370","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T14:19:52Z","timestamp":1730125192000},"page":"3970-3991","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Preclinical models for evaluating psychedelics in the treatment of major depressive disorder"],"prefix":"10.1111","volume":"183","author":[{"given":"Laith","family":"Alexander","sequence":"first","affiliation":[{"name":"Department of Psychological Medicine Institute of Psychiatry, Psychology and Neuroscience, King's College London  London UK"},{"name":"South London and the Maudsley NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dasha","family":"Anderson","sequence":"additional","affiliation":[{"name":"School of Physiology, Pharmacology &amp; Neuroscience University of Bristol  Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Baxter","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine Institute of Psychiatry, Psychology and Neuroscience, King's College London  London UK"},{"name":"South London and the Maudsley NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Claydon","sequence":"additional","affiliation":[{"name":"School of Physiology, Pharmacology &amp; Neuroscience University of Bristol  Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Rucker","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine Institute of Psychiatry, Psychology and Neuroscience, King's College London  London UK"},{"name":"South London and the Maudsley NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1299-6541","authenticated-orcid":false,"given":"Emma S. 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