Dopamine D2High receptors stimulated by phencyclidines, lysergic acid diethylamide, salvinorin A, and modafinil.
Philip Seeman, Hong-Chang Guan, Hélène Hirbec
Synapse August 1, 2009 DOI: 10.1002/syn.20647 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Laboratory experiment Peer reviewed |
|---|---|
| Population | Rat brain striatum homogenates |
| Interventions | Phencyclidine dopamine salvinorin A lysergic acid diethylamide (LSD) R-modafinil dizocilpine ketamine S-modafinil |
| Topics | LSD Salvia divinorum |
| Keywords | Pcp phencyclidine Modafinil Brain receptors Neural receptors Neuropharmacology psychopharmacology Brain activity Drug effects Receptor activation Stimulation Psychoactive substances hallucinogens Psychostimulants |
| Citations | 83 |
| Key findings | Phencyclidine and other psychostimulants and hallucinogens can stimulate dopamine D2 receptors in rat striatum at concentrations relevant to their behavioral actions. |
Abstract
Although it is commonly stated that phencyclidine is an antagonist at ionotropic glutamate receptors, there has been little measure of its potency on other receptors in brain tissue. Although we previously reported that phencyclidine stimulated cloned-dopamine D2Long and D2Short receptors, others reported that phencyclidine did not stimulate D2 receptors in homogenates of rat brain striatum. This study, therefore, examined whether phencyclidine and other hallucinogens and psychostimulants could stimulate the incorporation of [(35)S]GTP-gamma-S into D2 receptors in homogenates of rat brain striatum, using the same conditions as previously used to study the cloned D2 receptors. Using 10 microM dopamine to define 100% stimulation, phencyclidine elicited a maximum incorporation of 46% in rat striata, with a half-maximum concentration of 70 nM for phencyclidine, when compared with 80 nM for dopamine, 89 nM for salvinorin A (48 nM for D2Long), 105 nM for lysergic acid diethylamide (LSD), 120 nM for R-modafinil, 710 nM for dizocilpine, 1030 nM for ketamine, and >10,000 nM for S-modafinil. These compounds also inhibited the binding of the D2-selective ligand [(3)H]domperidone. The incorporation was inhibited by the presence of 200 microM guanylylimidodiphosphate and also by D2 blockade, using 10 microM S-sulpiride, but not by D1 blockade with 10 microM SCH23390. Hypertonic buffer containing 150 mM NaCl inhibited the stimulation by phencyclidine, which may explain negative results by others. It is concluded that phencyclidine and other psychostimulants and hallucinogens can stimulate dopamine D2 receptors at concentrations related to their behavioral actions.
Comparable studies
Other experimental studies on salvia divinorum, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. | 2002 | Experimental study | |
| Salvinorin A, an active component of the hallucinogenic sage salvia divinorum is a highly efficacious kappa-opioid receptor agonist: structural and functional considerations. Cloned human kappa-opioid receptors expressed in human embryonic kidney-293 cells and... | 2004 | Experimental study | |
| Synthesis and κ-opioid receptor activity of furan-substituted salvinorin A analogues. Animal model | 2014 | Experimental study | |
| Identification of the molecular mechanisms by which the diterpenoid salvinorin A binds to kappa-opioid receptors. | 2005 | Experimental study | |
| Structure-based design, synthesis, and biochemical and pharmacological characterization of novel salvinorin A analogues as active state probes of the kappa-opioid receptor. | 2009 | Experimental study |
Citations in the library
Cited by 33
- d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology International Journal of Molecular Sciences November 23, 2016
- Effects of hallucinogenic agents mescaline and phencyclidine on zebrafish behavior and physiology Progress in Neuro-Psychopharmacology and Biological Psychiatry January 10, 2012
- Neuropharmacology of the naturally occurring kappa-opioid hallucinogen salvinorin A. Pharmacological Reviews June 1, 2011
- Pharmacology of Hallucinations: Several Mechanisms for One Single Symptom? BioMed Research International 2014
- Pharmacological activity of salvinorin A, the major component of Salvia divinorum. Pharmacological Reports 2011
and 28 more in the library
Cites 10
- Recent advances in the phencyclidine model of schizophrenia American Journal of Psychiatry October 1, 1991
- Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proceedings of the National Academy of Sciences September 3, 2002
- Salvinorin A, an active component of the hallucinogenic sage salvia divinorum is a highly efficacious kappa-opioid receptor agonist: structural and functional considerations. Journal of Pharmacology and Experimental Therapeutics March 1, 2004
- Effects of salvinorin A on locomotor sensitization to D2/D3 dopamine agonist quinpirole. Neuroscience Letters December 3, 2008
- Phencyclidine and glutamate agonist LY379268 stimulate dopamine D2High receptors: D2 basis for schizophrenia. Synapse November 2008
and 5 more in the library