Dopamine D2High receptors stimulated by phencyclidines, lysergic acid diethylamide, salvinorin A, and modafinil
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 re...
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Published in | Synapse (New York, N.Y.) Vol. 63; no. 8; pp. 698 - 704 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.08.2009
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Subjects | |
Online Access | Get full text |
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Summary: | 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 [35S]GTP‐γ‐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 μM 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 [3H]domperidone. The incorporation was inhibited by the presence of 200 μM guanylylimidodiphosphate and also by D2 blockade, using 10 μM S‐sulpiride, but not by D1 blockade with 10 μM 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. Synapse 63:698–704, 2009. © 2009 Wiley‐Liss, Inc. |
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Bibliography: | Essel Foundation Veterans Health Services and Research Administration, Department of Veterans Affair Ontario Mental Health Foundation ArticleID:SYN20647 Comprehensive Epilepsy Program NINDS/NIMH Constance E. Lieber and Stephen Lieber VA West Los Angeles Healthcare Center, Los Angeles - No. CA 90073 Tourette Syndrome Association istex:3E22CEFCE1917D12472C4CF96143530F8733B646 O'Rorke family Dystonia Medical Research Foundation Dr. Karolina Jus estate National Neurological Research Specimen Bank National Multiple Sclerosis Society ark:/67375/WNG-N3TMT52Q-6 Medland family Hereditary Disease Foundation Rockert family ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 |
ISSN: | 0887-4476 1098-2396 1098-2396 |
DOI: | 10.1002/syn.20647 |