LSD-stimulated behaviors in mice require β-arrestin 2 but not β-arrestin 1
Scientific Reports September 5, 2021 Ramona M. Rodriguiz, Vineet Nadkarni, Christopher R. Means et al. 92 citations
Lysergic acid diethylamide (LSD) produces psychedelic effects through the 5-HT2A serotonin receptor, which activates both Gq and β-arrestin signaling pathways. Using mice lacking either β-arrestin1 or β-arrestin2, researchers found that LSD stimulated motor activities and psychedelic-like behaviors—including head twitches, grooming, retrograde walking, and nose-poking—in normal mice and those missing β-arrestin1, but not in mice missing β-arrestin2. The 5-HT2A antagonist MDL100907 blocked these effects. LSD also disrupted prepulse inhibition in normal and β-arrestin1-knockout mice, but not in β-arrestin2-knockouts. These findings indicate that LSD's psychedelic actions require β-arrestin2 signaling.