(+)Lysergic acid diethylamide, but not its nonhallucinogenic congeners, is a potent serotonin 5HT1C receptor agonist.
Kevin D. Burris, M Breeding, Elaine Sanders‐bush
Journal of Pharmacology and Experimental Therapeutics September 1, 1991 DOI: 10.1016/s0022-3565(25)20333-0 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro pharmacological study Peer reviewed |
|---|---|
| Population | Rat choroid plexus tissue and cultured rat choroid plexus epithelial cells |
| Topics | LSD Serotonin |
| Keywords | Choroid plexus Cerebral cortex Animals Rats, inbred strains Tritium Inositol phosphates Lisuride Receptors, serotonin Hydrolysis Male |
| Key points | The authors report that (+)LSD is a potent agonist at 5HT1C receptors, stimulating phosphoinositide hydrolysis with EC50 values of 9 nM in intact rat choroid plexus and 26 nM in cultured epithelial cells, while the nonhallucinogenic congeners (+)-2-bromo-LSD and lisuride did not activate these receptors. They propose that 5HT1C receptor activation may contribute to LSD's psychoactive effects. |
Abstract
Activation of central serotonin 5HT2 receptors is believed to be the primary mechanism whereby lysergic acid diethylamide (LSD) and other hallucinogens induce psychoactive effects. This hypothesis is based on extensive radioligand binding and electrophysiological and behavioral studies in laboratory animals. However, the pharmacological profiles of 5HT2 and 5HT1C receptors are similar, making it difficult to distinguish between effects due to activation of one or the other receptor. For this reason, it was of interest to investigate the interaction of LSD with 5HT1C receptors. Agonist-stimulated phosphoinositide hydrolysis in rat choroid plexus was used as a direct measure of 5HT1C receptor activation. (+)LSD potently stimulated phosphoinositide hydrolysis in intact choroid plexus and in cultures of choroid plexus epithelial cells, with EC50 values of 9 and 26 nM, respectively. The effect of (+)LSD in both systems was blocked by 5HT receptor antagonists with an order of activity consistent with interaction at 5HT1C receptors. Neither (+)-2-bromo-LSD nor lisuride, two nonhallucinogenic congeners of LSD, were able to stimulate 5HT1C receptors in cultured cells or intact choroid plexus. In contrast, lisuride, like (+)LSD, is a partial agonist at 5HT2 receptors in cerebral cortex slices and in NIH 3T3 cells transfected with 5HT2 receptor cDNA. The present finding that (+)LSD, but not its nonhallucinogenic congeners, is a 5HT1C receptor agonist suggests a possible role for these receptors in mediating the psychoactive effects of LSD.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 32
- A Single Dose of Lysergic Acid Diethylamide Influences Gene Expression Patterns within the Mammalian Brain Neuropsychopharmacology May 1, 2002
- Biosynthesis and Extracellular Concentrations of N,N-dimethyltryptamine (DMT) in Mammalian Brain. Scientific Reports June 27, 2019
- The serotonin 2C receptor potently modulates the head-twitch response in mice induced by a phenethylamine hallucinogen Psychopharmacology February 19, 2010
- Effect of Hallucinogens on Unconditioned Behavior Current Topics in Behavioral Neurosciences 2016
- LSD but not lisuride disrupts prepulse inhibition in rats by activating the 5-HT2A receptor Psychopharmacology November 24, 2009
and 27 more in the library