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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Rodriguiz, RM; Nadkarni, V; Means, CR; Pogorelov, VM; Chiu, Y-T; Roth, BL; Wetsel, WC

Published Date

  • September 3, 2021

Published In

Volume / Issue

  • 11 / 1

Start / End Page

  • 17690 -

PubMed ID

  • 34480046

Pubmed Central ID

  • PMC8417039

Electronic International Standard Serial Number (EISSN)

  • 2045-2322

Digital Object Identifier (DOI)

  • 10.1038/s41598-021-96736-3

Language

  • eng

Conference Location

  • England