Lysergic acid diethylamide (LSD) is a partial agonist of D2 dopaminergic receptors and it potentiates dopamine-mediated prolactin secretion in lactotrophs in vitro
Sabrina Giacomelli, Maura Palmery, Luca Romanelli, C. Yan Cheng, Bruno Silvestrini
Life Sciences June 1, 1998 DOI: 10.1016/s0024-3205(98)00262-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro study Peer reviewed |
|---|---|
| Population | Primary cultures of rat pituitary cells |
| Interventions | LSD dopamine bromocriptine spiperone SKF83566 cyproheptadine |
| Dose | 1.7x10(-9) M IC50; 10(-8)-10(-6) M; 10(-13)-10(-10) M; 10(-7) M dopamine; 10(-11) M bromocriptine |
| Topics | LSD |
| Keywords | Dopaminergic Prolactin cell Bromocriptine Agonist Pharmacology Endocrinology Dopamine receptor d2 Spiperone |
| Citations | 51 |
| Key points | LSD acts as a partial agonist at D2 dopamine receptors on lactotrophs, inhibiting prolactin secretion less potently than dopamine and showing both antagonistic and potentiating effects depending on concentration. |
Abstract
The hallucinogenic effects of lysergic acid diethylamide (LSD) have mainly been attributed to the interaction of this drug with the serotoninergic system, but it seems more likely that they are the result of the complex interactions of the drug with both the serotoninergic and dopaminergic systems. The aim of the present study was to investigate the functional actions of LSD at dopaminergic receptors using prolactin secretion by primary cultures of rat pituitary cells as a model. LSD produced a dose-dependent inhibition of prolactin secretion in vitro with an IC50 at 1.7x10(-9) M. This action was antagonized by spiperone but not by SKF83566 or cyproheptadine, which indicates that LSD has a specific effect on D2 dopaminergic receptors. The maximum inhibition of prolactin secretion achieved by LSD was lower than that by dopamine (60% versus 80%). Moreover, the fact that LSD at 10(-8)-10(-6) M antagonized the inhibitory effect of dopamine (10(-7) M) and bromocriptine (10(-11) M) suggests that LSD acts as a partial agonist at D2 receptors on lactotrophs in vitro. Interestingly, LSD at 10(-13)-10(-10) M, the concentrations which are 10-1000-fold lower than those required to induce direct inhibition on pituitary prolactin secretion, potentiated the dopamine (10(-10)-2.5x10(-9) M)-mediated prolactin secretion by pituitary cells in vitro. These results suggest that LSD not only interacts with dopaminergic receptors but also has a unique capacity for modulating dopaminergic transmission. These findings may offer new insights into the hallucinogenic effect of LSD.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 35
- Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects Biological Psychiatry November 29, 2014
- Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. European Neuropsychopharmacology May 20, 2016
- The effects of microdose LSD on time perception: a randomised, double-blind, placebo-controlled trial Psychopharmacology November 26, 2018
- A Single Dose of Lysergic Acid Diethylamide Influences Gene Expression Patterns within the Mammalian Brain Neuropsychopharmacology May 1, 2002
- d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology International Journal of Molecular Sciences November 23, 2016
and 30 more in the library
Cites 7
- Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sciences December 17, 1984
- Lysergic acid diethylamide: evidence for stimulation of cerebral dopamine receptors Brain Research August 1, 1975
- Lysergic Acid Diethylamide (LSD) and Lisuride: Differentiation of Their Neuropharmacological Actions Science April 30, 1982
- Lysergic acid diethylamide is a partial agonist at 5-HT2 receptors in ovine uterine artery of late pregnancy European Journal of Pharmacology January 5, 1993
- LSD-Induced Decrease in Serum Prolactin in Rats Experimental Biology and Medicine September 1, 1971
and 2 more in the library