Effects of a psychedelic 5-HT2A receptor agonist on anxiety-related behavior and fear processing in mice.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology June 1, 2022 Błażej D Pędzich, Sarah Rubens, Mehdi Sekssaoui et al.
Activation of the serotonin 2A (5-HT2A) receptor suppresses fear expression but does not affect retention of fear extinction. Using the psychedelic DOI in mice, the authors found that 5-HT2A receptor activation reduced anxiety-like avoidance behavior and diminished fear expression in multiple tasks, including passive avoidance and auditory fear conditioning. The effect depended on 5-HT2A receptors in the amygdala: local infusion of a 5-HT2A antagonist into the amygdala reversed the effect, while local DOI infusion into the amygdala was sufficient to suppress fear expression. These findings clarify a neural mechanism by which psychedelics may reduce fear, but provide no evidence that they enhance fear extinction memory.