The serotonergic hallucinogen 5-methoxy-N,N-dimethyltryptamine disrupts cortical activity in a regionally-selective manner via 5-HT1A and 5-HT2A receptors

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) reduced low frequency cortical oscillations (LFCO) in the prefrontal cortex of both wild type and serotonin 2A receptor knockout mice.

• 5-MeO-DMT diminished LFCO in the prefrontal cortex, visual, somatosensory, and auditory cortices.
• The reduction of LFCO in the prefrontal cortex of knockout mice was fully prevented by the serotonin 1A receptor antagonist WAY-100635.
• 5-MeO-DMT decreased serotonin release in the prefrontal cortex primarily through serotonin 1A receptor activation.
• In wild type mice, 5-MeO-DMT disrupted activity in sensory cortices, while effects in knockout mice were limited to the visual cortex.
• Antipsychotic drugs reversed the effects of 5-MeO-DMT in wild type mice, suggesting a potential model for antipsychotic drug development.

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