Serotonin and hallucinogens.
George K. Aghajanian, Gerard J. Marek
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology August 1999 DOI: 10.1016/s0893-133x(98)00135-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Serotonin |
| Key findings | Proposes that psychedelic hallucinogens act as partial agonists at 5-HT2A receptors, and that a 5-HT2A-mediated enhancement of glutamatergic transmission in the cerebral cortex may explain their cognitive, perceptual, and affective effects. |
Abstract
This brief review traces the serotonin (5-HT) hypothesis of the action of hallucinogenic drugs from the early 1950s to the present day. There is now converging evidence from biochemical, electrophysiological, and behavioral studies that the two major classes of psychedelic hallucinogens, the indoleamines (e.g., LSD) and the phenethylamines (e.g., mescaline), have a common site of action as partial agonists at 5-HT2A and other 5-HT2 receptors in the central nervous system. The noradrenergic locus coeruleus and the cerebral cortex are among the regions where hallucinogens have prominent effects through their actions upon a 5-HT2A receptors. Recently, we have observed a novel effect of hallucinogens--a 5-HT2A receptor-mediated enhancement of nonsynchronous, late components of glutamatergic excitatory postsynaptic potentials at apical dendrites of layer V cortical pyramidal cells. We propose that an effect of hallucinogens upon glutamatergic transmission in the cerebral cortex may be responsible for the higher-level cognitive, perceptual, and affective distortions produced by these drugs.