Scn2a-deficient mice exhibit serotonergic dysfunction and altered behavioral responses to psilocybin

Psilocybin increases sociability in Scn2a-deficient mice without changing anxiety-like behavior, while wild-type mice show decreased anxiety-like behavior without increased sociability.

• Why it matters: Social deficits are central to ASD, and serotonergic psychedelics like psilocybin may modulate social behavior, but genotype-linked differences in response are unclear.
• What they did: The study compared psilocybin behavioral effects in Scn2a-deficient versus wild-type mice and measured head twitch responses, serotonin levels, receptor expression in the mPFC, and spontaneous firing in the Dorsal Raphe Nucleus.
• The result: Scn2a-deficient mice had a reduced head twitch response after psilocybin, altered mPFC serotonin receptor expression despite unchanged baseline serotonin, and increased spontaneous firing, supporting genotype-linked serotonergic dysfunction.

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