5-HT2ARs Mediate Therapeutic Behavioral Effects of Psychedelic Tryptamines.
ACS chemical neuroscience February 1, 2023 Lindsay P Cameron, Seona D Patel, Maxemiliano V Vargas et al. 113 citations
Activation of serotonin 2A receptors (5-HT2ARs) is essential for tryptamine-based psychedelics to produce antidepressant-like effects in rodents. While hallucinogenic properties are generally attributed to 5-HT2AR activation, it was unclear whether these receptors also mediate antidepressant effects, especially because some nonhallucinogenic analogues show antidepressant-like properties. Using pharmacological and genetic tools, the authors demonstrate that 5-HT2AR activation is required for the antidepressant-like effects of tryptamine psychedelics, suggesting that hallucinogenic and therapeutic effects can arise through the same receptor.