{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:38:30Z","timestamp":1791409110598,"version":"4.3.3"},"reference-count":48,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,25]],"date-time":"2023-06-25T00:00:00Z","timestamp":1687651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Anxiety is a serious mental disorder, and recent statistics have determined that 35.12% of the global population had an anxiety disorder during the COVID-19 pandemic. A mechanism associated with anxiolytic effects is related to nicotinic acetylcholine receptor (nAChR) agonists, principally acting on the \u03b14\u03b22 nAChR subtype. nAChRs are present in different animal models, including murine and teleosteos ones. Zebrafish has become an ideal animal model due to its high human genetic similarities (70%), giving it high versatility in different areas of study, among them in behavioral studies related to anxiety. The novel tank diving test (NTT) is one of the many paradigms used for studies on new drugs related to their anxiolytic effect. In this work, an adult zebrafish was used to determine the behavioral effects of 3- and 5-halocytisine derivatives, using the NTT at different doses. Our results show that substitution at position 3 by chlorine or bromine decreases the time spent by the fish at the bottom compared to the control. However, the 3-chloro derivative at higher doses increases the bottom dwelling time. In contrast, substitution at the 5 position increases bottom dwelling at all concentrations showing no anxiolytic effects in this model. Unexpected results were observed with the 5-chlorocytisine derivative, which at a concentration of 10 mg\/L produced a significant decrease in bottom dwelling and showed high times of freezing. In conclusion, the 3-chloro and 3-bromo derivatives show an anxiolytic effect, the 3-chlorocytisine derivative being more potent than the 3-bromo derivative, with the lowest time at the bottom of the tank at 1mg\/L. On the other hand, chlorine, and bromine at position 5 produce an opposite effect.<\/jats:p>","DOI":"10.3390\/ijms241310635","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T01:42:32Z","timestamp":1687743752000},"page":"10635","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Behavioral Study of 3- and 5-Halocytisine Derivatives in Zebrafish Using the Novel Tank Diving Test (NTT)"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5468-4936","authenticated-orcid":false,"given":"Amaury","family":"Far\u00edas-Cea","sequence":"first","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda Molecular y Qu\u00edmica Medicinal, Departamento de Ciencias Qu\u00edmica y Recursos Naturales, Facultad de Ingenier\u00eda y Ciencias, Universidad de La Frontera, Temuco 4811230, Chile"},{"name":"Programa de Doctorado en Ciencias de Recursos Naturales, Universidad de la Frontera, Temuco 4811230, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crist\u00f3bal","family":"Leal","sequence":"additional","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda Molecular y Qu\u00edmica Medicinal, Departamento de Ciencias Qu\u00edmica y Recursos Naturales, Facultad de Ingenier\u00eda y Ciencias, Universidad de La Frontera, Temuco 4811230, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mart\u00edn","family":"H\u00f6dar-Salazar","sequence":"additional","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda Molecular y Qu\u00edmica Medicinal, Departamento de Ciencias Qu\u00edmica y Recursos Naturales, Facultad de Ingenier\u00eda y Ciencias, Universidad de La Frontera, Temuco 4811230, Chile"},{"name":"Programa de Doctorado en Ciencias menci\u00f3n Biolog\u00eda Celular y Molecular Aplicada, Universidad de La Frontera, Temuco 4811230, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Esparza","sequence":"additional","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda Molecular y Qu\u00edmica Medicinal, Departamento de Ciencias Qu\u00edmica y Recursos Naturales, Facultad de Ingenier\u00eda y Ciencias, Universidad de La Frontera, Temuco 4811230, Chile"},{"name":"Programa de Doctorado en Ciencias menci\u00f3n Biolog\u00eda Celular y Molecular Aplicada, Universidad de La Frontera, Temuco 4811230, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Mart\u00ednez-Duran","sequence":"additional","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda Molecular y Qu\u00edmica Medicinal, Departamento de Ciencias Qu\u00edmica y Recursos Naturales, Facultad de Ingenier\u00eda y Ciencias, Universidad de La Frontera, Temuco 4811230, Chile"},{"name":"Programa de Doctorado en Ciencias menci\u00f3n Biolog\u00eda Celular y Molecular Aplicada, Universidad de La Frontera, Temuco 4811230, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irma","family":"Fuentes","sequence":"additional","affiliation":[{"name":"Instituto de Ciencias Aplicadas, Facultad de Ingenier\u00eda, Universidad Aut\u00f3noma de Chile, Temuco 4810101, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0553-1014","authenticated-orcid":false,"given":"Patricio","family":"Iturriaga-V\u00e1squez","sequence":"additional","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda Molecular y Qu\u00edmica Medicinal, Departamento de Ciencias Qu\u00edmica y Recursos Naturales, Facultad de Ingenier\u00eda y Ciencias, Universidad de La Frontera, Temuco 4811230, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association (2013). 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