Classical psychedelic drugs show promise as a treatment for major depressive disorder and related psychiatric disorders. This therapeutic efficacy stems from long-lasting psychedelic-induced neuroplasticity onto prefrontal cortical neurons and is thought to require the postsynaptic expression of serotonin 2A receptors (5-HT_2AR). However, other cortical regions such as the granular...
ABSTRACT Classical psychedelic drugs are thought to increase excitability of pyramidal cells in prefrontal cortex via activation of serotonin 2 A receptors (5-HT2 A Rs). Here, we instead find that multiple classes of psychedelics dose-dependently suppress intrinsic excitability of pyramidal neurons, and that extracellular delivery of psychedelics decreases excitability significantly more than...