Psychedelic 4-AcO-DMT reduces fear-freezing by activating decision-area neurons in mice

4-acetoxy-N,N-dimethyltryptamine (4-AcO-DMT) significantly reduced looming-induced freezing behavior compared to R/S-MDMA.

• The compound 4-AcO-DMT did not produce overt hallucinogenic effects in the experimental conditions.
• The reduction in freezing behavior is associated with decreased innate fear emotion.
• The anti-fear effect of 4-AcO-DMT is independent of specific signaling pathways and visual function.
• 4-AcO-DMT activates certain neurons in the prelimbic cortex through specific receptors.
• The findings suggest a robust anti-innate fear effect of psychedelics, revealing new aspects of their emotional modulation.

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