{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:56:59Z","timestamp":1790776619383,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM136906"],"award-info":[{"award-number":["R01GM136906"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Thigmotaxis, or edge preference, is widely used as a measure of anxiety in vertebrate model systems. However, variability in this behavior limits its utility as a scalable measure for anxiolytic drug discovery. In the current study, we examine caffeine\u2010induced thigmotaxis, using 5\u2010day\u2010old zebrafish larvae as a model system.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>We modified our imaging system and AI\u2010assisted analysis for measurements of behavior in six\u2010well plates. The imaging system was used to measure thigmotaxis and several other behaviors, including overall activity, scoot and burst swimming, and responses to acoustic and visual stimuli.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>Caffeine (100\u00a0mg\/L) caused the zebrafish larvae to exhibit increased edge preference, decreased activity, increased scooting, and decreased bursting behavior. Coadministration with diazepam (0.25\u00a0mg\/L), a central nervous system depressant, significantly reduced caffeine\u2010induced thigmotaxis and increased locomotor activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings support edge preference as a reliable measure of anxiety and reconcile existing conflicting results regarding diazepam's anxiolytic efficacy in zebrafish larvae, suggesting that anxiolytic effects are most pronounced against a heightened anxiety baseline. These findings also establish a robust platform for high\u2010throughput identification of anxiolytic compounds with potential relevance for treating anxiety and related stress in humans.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71769","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:07:21Z","timestamp":1790773641000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Brewing Anxiety: Caffeine\u2010Induced Thigmotaxis in Zebrafish Larvae"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9739-965X","authenticated-orcid":false,"given":"Rishi","family":"Rai","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, Cell Biology and Biochemistry Brown University  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thais","family":"Del Rosario Hernandez","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Cell Biology and Biochemistry Brown University  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robbert","family":"Creton","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Cell Biology and Biochemistry Brown University  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"National Institute of Mental Health (NIMH). n.d. \u201cAny Anxiety Disorder.\u201d Accessed January 4 2026.https:\/\/www.nimh.nih.gov\/health\/statistics\/any\u2010anxiety\u2010disorder."},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000040"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2009.07.009"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0615\u201007.2007"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2010.140"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706796"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ntt.2011.08.010"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2020.111747"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159x19666211111142027"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1089\/zeb.2014.0989"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1515\/RNS.2011.008"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.116096"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2009.06.022"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0031\u20106997(24)01396\u20106"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0074\u20107742(05)63007\u20103"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2019.134548"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010023\u201030303\u2010w"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2013.12.002"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.307"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2024.115151"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2024.1270246"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742\u20107843.2011.00710.x"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2013.10.042"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2011.08.040"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/1559827620973936"},{"key":"e_1_2_10_27_1","unstructured":"Rai 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