Control of Serotonergic Function in Medial Prefrontal Cortex by Serotonin-2A Receptors through a Glutamate-Dependent Mechanism
Journal of Neuroscience December 15, 2001 Raúl Martín‐Ruiz, M. Victoria Puig, Pau Celada et al. 335 citations
The hallucinogen DOI suppresses the firing rate of most serotonergic neurons in the dorsal raphe nucleus and reduces serotonin release in the medial prefrontal cortex to 33% of baseline, effects mediated by 5-HT2A receptors and reversed by a GABA-A antagonist. However, locally applied DOI in the medial prefrontal cortex increases serotonin release to 164% of baseline through AMPA receptors, not NMDA receptors. DOI also increases the firing rate of a subgroup of serotonergic neurons, indicating enhanced output of pyramidal neurons. Pyramidal neurons coexpress 5-HT1A and 5-HT2A receptors, and DOI disrupts the balance between excitatory and inhibitory inputs, leading to increased activity that may mediate its hallucinogenic action.