{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:03:50Z","timestamp":1792789430888,"version":"4.5.0"},"reference-count":67,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T00:00:00Z","timestamp":1668556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Back of the Yards algae sciences (BYAS)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>There is increasing interest in the therapeutic potential of psilocybin. In rodents, the serotonin precursor, 5-hydroxytryptophan (5-HTP) and psilocybin induce a characteristic 5-HT2A receptor (5-HT2AR)-mediated head twitch response (HTR), which is correlated with the human psychedelic trip. We examined the role of other serotonergic receptors and the trace amine -associated receptor 1 (TAAR1) in modulating 5-HTP- and psilocybin-induced HTR. Male C57BL\/6J mice (11 weeks, ~30 g) were administered 5-HTP, 50\u2013250 mg\/kg i.p., 200 mg\/kg i.p. after pretreatment with 5-HT\/TAAR1 receptor modulators, psilocybin 0.1\u201325.6 mg\/kg i.p. or 4.4 mg\/kg i.p., immediately preceded by 5-HT\/TAAR1 receptor modulators. HTR was assessed in a custom-built magnetometer. 5-HTP and psilocybin induced a dose-dependent increase in the frequency of HTR over 20 min with attenuation by the 5-HT2AR antagonist, M100907, and the 5-HT1AR agonist, 8-OH-DPAT. The 5-HT2CR antagonist, RS-102221, enhanced HTR at lower doses but reduced it at higher doses. The TAAR1 antagonist, EPPTB, reduced 5-HTP- but not psilocybin-induced HTR. We have confirmed the key role of 5-HT2AR in HTR, an inhibitory effect of 5-HT1AR, a bimodal contribution of 5-HT2CR and a role of TAAR1 in modulating HTR induced by 5-HTP. Compounds that modulate psychedelic-induced HTR have important potential in the emerging therapeutic use of these compounds.<\/jats:p>","DOI":"10.3390\/ijms232214148","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T03:05:21Z","timestamp":1668654321000},"page":"14148","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Role of 5-HT2A, 5-HT2C, 5-HT1A and TAAR1 Receptors in the Head Twitch Response Induced by 5-Hydroxytryptophan and Psilocybin: Translational Implications"],"prefix":"10.3390","volume":"23","author":[{"given":"Orr","family":"Shahar","sequence":"first","affiliation":[{"name":"Biological Psychiatry Laboratory and Hadassah BrainLabs, Hadassah Medical Center, Hebrew University Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6331-7174","authenticated-orcid":false,"given":"Alexander","family":"Botvinnik","sequence":"additional","affiliation":[{"name":"Biological Psychiatry Laboratory and Hadassah BrainLabs, Hadassah Medical Center, Hebrew University Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noam","family":"Esh-Zuntz","sequence":"additional","affiliation":[{"name":"Biological Psychiatry Laboratory and Hadassah BrainLabs, Hadassah Medical Center, Hebrew University Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Brownstien","sequence":"additional","affiliation":[{"name":"Biological Psychiatry Laboratory and Hadassah BrainLabs, Hadassah Medical Center, Hebrew University Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Wolf","sequence":"additional","affiliation":[{"name":"Biological Psychiatry Laboratory and Hadassah BrainLabs, Hadassah Medical Center, Hebrew University Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7628-0975","authenticated-orcid":false,"given":"Amit","family":"Lotan","sequence":"additional","affiliation":[{"name":"Biological Psychiatry Laboratory and Hadassah BrainLabs, Hadassah Medical Center, Hebrew University Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilly","family":"Wolf","sequence":"additional","affiliation":[{"name":"Biological Psychiatry Laboratory and Hadassah BrainLabs, Hadassah Medical Center, Hebrew University Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9914-632X","authenticated-orcid":false,"given":"Bernard","family":"Lerer","sequence":"additional","affiliation":[{"name":"Biological Psychiatry Laboratory and Hadassah BrainLabs, Hadassah Medical Center, Hebrew University Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzuri","family":"Lifschytz","sequence":"additional","affiliation":[{"name":"Biological Psychiatry Laboratory and Hadassah BrainLabs, Hadassah Medical Center, Hebrew University Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/wps.20692","article-title":"Economics and mental health: The current scenario","volume":"19","author":"Knapp","year":"2020","journal-title":"World Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100341","DOI":"10.1016\/j.lanepe.2022.100341","article-title":"The burden of mental disorders, substance use disorders and self-harm among young people in Europe, 1990\u20132019: Findings from the Global Burden of Disease Study 2019","volume":"16","author":"Castelpietra","year":"2022","journal-title":"Lancet Reg. 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