LSD and DOB: interaction with 5‐HT2A receptors to inhibit NMDA receptor‐mediated transmission in the rat prefrontal cortex
European Journal of Neuroscience September 1, 1999 Viktor L. Arvanov, Xiaofu Liang, Angelo Russo et al. 64 citations
Hallucinogenic compounds, including the phenethylamine DOB (a selective serotonin 5-HT2A,2C receptor agonist) and the indoleamine LSD (which binds to multiple serotonin, dopamine, and adrenergic receptors), inhibit NMDA receptor-mediated currents and synaptic responses in pyramidal cells of prefrontal cortical slices, while non-hallucinogenic congeners do not. This inhibition is mimicked by serotonin when 5-HT1A and 5-HT3 receptors are blocked, and is prevented by 5-HT2A receptor antagonists. At low concentrations, LSD and DOB partially depress the NMDA response and block serotonin's inhibitory effect, indicating partial agonist action. The inhibition depends on a Ca2+/calmodulin-dependent protein kinase II pathway, not protein kinase C. The findings suggest hallucinogens may alter sensory, perceptual, affective, and cognitive processes by modulating NMDA receptors through 5-HT2A receptor partial agonism.