LSD-stimulated behaviors in mice require β-arrestin 2 but not β-arrestin 1

Abstract Recent evidence suggests that psychedelic drugs can exert beneficial effects on anxiety, depression, and ethanol and nicotine abuse in humans. However, their hallucinogenic side-effects often preclude their clinical use. Lysergic acid diethylamide (LSD) is a prototypical hallucinogen and it...

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Autores principales:	Ramona M. Rodriguiz, Vineet Nadkarni, Christopher R. Means, Vladimir M. Pogorelov, Yi-Ting Chiu, Bryan L. Roth, William C. Wetsel
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3215b394370e440fb5ba82da17d03128
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spelling	oai:doaj.org-article:3215b394370e440fb5ba82da17d031282021-12-02T15:29:02ZLSD-stimulated behaviors in mice require β-arrestin 2 but not β-arrestin 110.1038/s41598-021-96736-32045-2322https://doaj.org/article/3215b394370e440fb5ba82da17d031282021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96736-3https://doaj.org/toc/2045-2322Abstract Recent evidence suggests that psychedelic drugs can exert beneficial effects on anxiety, depression, and ethanol and nicotine abuse in humans. 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-HT2A serotonin receptor (5-HT2AR). 5-HT2AR activation stimulates Gq- and β-arrestin- (βArr) mediated signaling. To separate these signaling modalities, we have used βArr1 and βArr2 mice. We find that LSD stimulates motor activities to similar extents in WT and βArr1-KO mice, without effects in βArr2-KOs. LSD robustly stimulates many surrogates of psychedelic drug actions including head twitches, grooming, retrograde walking, and nose-poking in WT and βArr1-KO animals. By contrast, in βArr2-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 βArr1-KOs, but not in βArr2-KOs. MDL restores LSD-mediated disruption of PPI in WT mice; haloperidol is required for normalization of PPI in βArr1-KOs. Collectively, these results reveal that LSD’s psychedelic drug-like actions appear to require βArr2.Ramona M. RodriguizVineet NadkarniChristopher R. MeansVladimir M. PogorelovYi-Ting ChiuBryan L. RothWilliam C. WetselNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ramona M. Rodriguiz Vineet Nadkarni Christopher R. Means Vladimir M. Pogorelov Yi-Ting Chiu Bryan L. Roth William C. Wetsel LSD-stimulated behaviors in mice require β-arrestin 2 but not β-arrestin 1
description	Abstract Recent evidence suggests that psychedelic drugs can exert beneficial effects on anxiety, depression, and ethanol and nicotine abuse in humans. 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-HT2A serotonin receptor (5-HT2AR). 5-HT2AR activation stimulates Gq- and β-arrestin- (βArr) mediated signaling. To separate these signaling modalities, we have used βArr1 and βArr2 mice. We find that LSD stimulates motor activities to similar extents in WT and βArr1-KO mice, without effects in βArr2-KOs. LSD robustly stimulates many surrogates of psychedelic drug actions including head twitches, grooming, retrograde walking, and nose-poking in WT and βArr1-KO animals. By contrast, in βArr2-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 βArr1-KOs, but not in βArr2-KOs. MDL restores LSD-mediated disruption of PPI in WT mice; haloperidol is required for normalization of PPI in βArr1-KOs. Collectively, these results reveal that LSD’s psychedelic drug-like actions appear to require βArr2.
format	article
author	Ramona M. Rodriguiz Vineet Nadkarni Christopher R. Means Vladimir M. Pogorelov Yi-Ting Chiu Bryan L. Roth William C. Wetsel
author_facet	Ramona M. Rodriguiz Vineet Nadkarni Christopher R. Means Vladimir M. Pogorelov Yi-Ting Chiu Bryan L. Roth William C. Wetsel
author_sort	Ramona M. Rodriguiz
title	LSD-stimulated behaviors in mice require β-arrestin 2 but not β-arrestin 1
title_short	LSD-stimulated behaviors in mice require β-arrestin 2 but not β-arrestin 1
title_full	LSD-stimulated behaviors in mice require β-arrestin 2 but not β-arrestin 1
title_fullStr	LSD-stimulated behaviors in mice require β-arrestin 2 but not β-arrestin 1
title_full_unstemmed	LSD-stimulated behaviors in mice require β-arrestin 2 but not β-arrestin 1
title_sort	lsd-stimulated behaviors in mice require β-arrestin 2 but not β-arrestin 1
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3215b394370e440fb5ba82da17d03128
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LSD-stimulated behaviors in mice require β-arrestin 2 but not β-arrestin 1

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