LSD and DOB: interaction with 5‐HT2A receptors to inhibit NMDA receptor‐mediated transmission in the rat prefrontal cortex
Viktor L. Arvanov, Xiaofu Liang, Angelo Russo, Rex Y. Wang
European Journal of Neuroscience September 1, 1999 DOI: 10.1046/j.1460-9568.1999.00726.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Laboratory experiment Peer reviewed |
|---|---|
| Population | Prefrontal cortical slices from rats |
| Interventions | DOB LSD serotonin M100907 ketanserin chelerythrine |
| Topics | Serotonin LSD |
| Keywords | Hallucinogen Nmda receptor Pharmacology Chelerythrine Inhibitory postsynaptic potential Ketanserin Partial agonist 5-HT Receptor 5-ht2 receptor Phenethylamine 5-ht1 receptor |
| Citations | 64 |
| Key findings | Hallucinogens LSD and DOB inhibit NMDA receptor-mediated currents and synaptic responses in prefrontal cortical pyramidal cells via 5-HT2A receptor partial agonism and a Ca2+/CaM-KII-dependent pathway. |
Abstract
Abstract Both the phenethylamine hallucinogen (–)‐1‐2,5‐dimethoxy‐4‐bromophenyl‐2‐aminopropane (DOB), a selective serotonin 5‐HT 2A,2C receptor agonist, and the indoleamine hallucinogen d ‐lysergic acid diethylamide (LSD, which binds to 5‐HT1A, 1B, 1D, 1E, 1F, 2A, 2C, 5, 6, 7, dopamine D 1 and D 2 , and α 1 and α 2 adrenergic receptors), but not their non‐hallucinogenic congeners, inhibited N‐methyl‐ d ‐aspartate (NMDA)‐induced inward current and NMDA receptor‐mediated synaptic responses evoked by electrical stimulation of the forceps minor in pyramidal cells of the prefrontal cortical slices. The inhibitory effect of hallucinogens was mimicked by 5‐HT in the presence of selective 5‐HT 1A and 5‐HT 3 receptor antagonists. The inhibitory action of DOB, LSD and 5‐HT on the NMDA transmission was blocked by the 5‐HT 2A receptor antagonists r ‐(+)‐α‐(2,3‐dimethoxyphenil)‐1‐[4‐fluorophenylethyl]‐4‐piperidinemethanol (M100907) and ketanserin. However, at low concentrations, when both LSD and DOB by themselves only partially depressed the NMDA response, they blocked the inhibitory effect of 5‐HT, suggesting a partial agonist action. Whereas N‐(4‐aminobutyl)‐5‐chloro‐2‐naphthalenesulphonamide (W‐7, a calmodulin antagonist) and N‐[2‐[[[3‐(4′‐chlorophenyl)‐ 2‐propenyl]methylamino]methyl]phenyl]‐N‐(2‐hydroxyethyl)‐4′‐methoxy‐benzenesulphonamide phosphate (KN‐93, a Ca 2+ /CaM‐KII inhibitor), but not the negative control 2‐[N‐4′methoxybenzenesulphonyl]amino‐N‐(4′‐chlorophenyl)‐2‐propenyl‐N‐methylbenzylamine phosphate (KN‐92), blocked the inhibitory action of LSD and DOB, the selective protein kinase C inhibitor chelerythrine was without any effect. We conclude that phenethylamine and indoleamine hallucinogens may exert their hallucinogenic effect by interacting with 5‐HT 2A receptors via a Ca 2+ /CaM‐KII‐dependent signal transduction pathway as partial agonists and modulating the NMDA receptors‐mediated sensory, perceptual, affective and cognitive processes.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 25
- Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin Scientific Reports April 19, 2017
- Transcriptome Fingerprints Distinguish Hallucinogenic and Nonhallucinogenic 5-Hydroxytryptamine 2A Receptor Agonist Effects in Mouse Somatosensory Cortex Journal of Neuroscience October 1, 2003
- d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology International Journal of Molecular Sciences November 23, 2016
- Lysergic acid diethylamide and [−]-2,5-dimethoxy-4-methylamphetamine increase extracellular glutamate in rat prefrontal cortex Brain Research August 27, 2004
- LSD but not lisuride disrupts prepulse inhibition in rats by activating the 5-HT2A receptor Psychopharmacology November 24, 2009
and 20 more in the library
Cites 9
- The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate British Journal of Pharmacology June 1, 1983
- Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sciences December 17, 1984
- Dose-Response Study of N,N-Dimethyltryptamine in Humans Archives of General Psychiatry February 1, 1994
- Lysergic acid diethylamide and 2,5-dimethoxy-4-methylamphetamine are partial agonists at serotonin receptors linked to phosphoinositide hydrolysis. Journal of Pharmacology and Experimental Therapeutics September 1, 1988
- Persistence of lysergic acid diethylamide in the plasma of human subjects Clinical Pharmacology & Therapeutics September 1, 1964
and 4 more in the library