| First Author | Rodriguiz RM | Year | 2021 |
| Journal | Sci Rep | Volume | 11 |
| Issue | 1 | Pages | 17690 |
| PubMed ID | 34480046 | Mgi Jnum | J:331223 |
| Mgi Id | MGI:6766265 | Doi | 10.1038/s41598-021-96736-3 |
| Citation | Rodriguiz RM, et al. (2021) LSD-stimulated behaviors in mice require beta-arrestin 2 but not beta-arrestin 1. Sci Rep 11(1):17690 |
| abstractText | 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 beta-arrestin- (betaArr) mediated signaling. To separate these signaling modalities, we have used betaArr1 and betaArr2 mice. We find that LSD stimulates motor activities to similar extents in WT and betaArr1-KO mice, without effects in betaArr2-KOs. LSD robustly stimulates many surrogates of psychedelic drug actions including head twitches, grooming, retrograde walking, and nose-poking in WT and betaArr1-KO animals. By contrast, in betaArr2-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 betaArr1-KOs, but not in betaArr2-KOs. MDL restores LSD-mediated disruption of PPI in WT mice; haloperidol is required for normalization of PPI in betaArr1-KOs. Collectively, these results reveal that LSD's psychedelic drug-like actions appear to require betaArr2. |
