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

Publication ,  Journal Article
Rodriguiz, RM; Nadkarni, V; Means, CR; Pogorelov, VM; Chiu, Y-T; Roth, BL; Wetsel, WC
Published in: Sci Rep
September 3, 2021

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.

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Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

September 3, 2021

Volume

11

Issue

1

Start / End Page

17690

Location

England

Related Subject Headings

  • beta-Arrestin 2
  • beta-Arrestin 1
  • Signal Transduction
  • Serotonin Receptor Agonists
  • Motor Activity
  • Mice, Knockout
  • Mice
  • Lysergic Acid Diethylamide
  • Grooming
  • Behavior, Animal
 

Citation

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Rodriguiz, R. M., Nadkarni, V., Means, C. R., Pogorelov, V. M., Chiu, Y.-T., Roth, B. L., & Wetsel, W. C. (2021). LSD-stimulated behaviors in mice require β-arrestin 2 but not β-arrestin 1. Sci Rep, 11(1), 17690. https://doi.org/10.1038/s41598-021-96736-3
Rodriguiz, Ramona M., Vineet Nadkarni, Christopher R. Means, Vladimir M. Pogorelov, Yi-Ting Chiu, Bryan L. Roth, and William C. Wetsel. “LSD-stimulated behaviors in mice require β-arrestin 2 but not β-arrestin 1.Sci Rep 11, no. 1 (September 3, 2021): 17690. https://doi.org/10.1038/s41598-021-96736-3.
Rodriguiz RM, Nadkarni V, Means CR, Pogorelov VM, Chiu Y-T, Roth BL, et al. LSD-stimulated behaviors in mice require β-arrestin 2 but not β-arrestin 1. Sci Rep. 2021 Sep 3;11(1):17690.
Rodriguiz, Ramona M., et al. “LSD-stimulated behaviors in mice require β-arrestin 2 but not β-arrestin 1.Sci Rep, vol. 11, no. 1, Sept. 2021, p. 17690. Pubmed, doi:10.1038/s41598-021-96736-3.
Rodriguiz RM, Nadkarni V, Means CR, Pogorelov VM, Chiu Y-T, Roth BL, Wetsel WC. LSD-stimulated behaviors in mice require β-arrestin 2 but not β-arrestin 1. Sci Rep. 2021 Sep 3;11(1):17690.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

September 3, 2021

Volume

11

Issue

1

Start / End Page

17690

Location

England

Related Subject Headings

  • beta-Arrestin 2
  • beta-Arrestin 1
  • Signal Transduction
  • Serotonin Receptor Agonists
  • Motor Activity
  • Mice, Knockout
  • Mice
  • Lysergic Acid Diethylamide
  • Grooming
  • Behavior, Animal