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However, their hallucinogenic side-effects often preclude their clinical use. Lysergic acid diethylamide (LSD) is a prototypical hallucinogen and its psychedelic actions are exerted through the 5-HT\n                    <jats:sub>2A<\/jats:sub>\n                    serotonin receptor (5-HT2AR). 5-HT2AR activation stimulates Gq- and \u03b2-arrestin- (\u03b2Arr) mediated signaling. To separate these signaling modalities, we have used \u03b2Arr1 and \u03b2Arr2 mice. We find that LSD stimulates motor activities to similar extents in WT and \u03b2Arr1-KO mice, without effects in \u03b2Arr2-KOs. LSD robustly stimulates many surrogates of psychedelic drug actions including head twitches, grooming, retrograde walking, and nose-poking in WT and \u03b2Arr1-KO animals. By contrast, in \u03b2Arr2-KO mice head twitch responses are low with LSD and this psychedelic is without effects on other surrogates. The 5-HT2AR antagonist MDL100907 (MDL) blocks the LSD effects. LSD also disrupts prepulse inhibition (PPI) in WT and \u03b2Arr1-KOs, but not in \u03b2Arr2-KOs. MDL restores LSD-mediated disruption of PPI in WT mice; haloperidol is required for normalization of PPI in \u03b2Arr1-KOs. Collectively, these results reveal that LSD\u2019s psychedelic drug-like actions appear to require \u03b2Arr2.\n                  <\/jats:p>","DOI":"10.1038\/s41598-021-96736-3","type":"journal-article","created":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T08:22:07Z","timestamp":1630657327000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":105,"title":["LSD-stimulated behaviors in mice require \u03b2-arrestin 2 but not \u03b2-arrestin 1"],"prefix":"10.1038","volume":"11","author":[{"given":"Ramona M.","family":"Rodriguiz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vineet","family":"Nadkarni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher R.","family":"Means","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir M.","family":"Pogorelov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ting","family":"Chiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan L.","family":"Roth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William C.","family":"Wetsel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,3]]},"reference":[{"key":"96736_CR1","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1124\/pr.115.011478","volume":"68","author":"DE Nichols","year":"2016","unstructured":"Nichols, D. 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