RRC ID 11857
Author Moreno JL, Holloway T, Albizu L, Sealfon SC, González-Maeso J.
Title Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists.
Journal Neurosci Lett
Abstract Hallucinogenic drugs, including mescaline, psilocybin and lysergic acid diethylamide (LSD), act at serotonin 5-HT2A receptors (5-HT2ARs). Metabotropic glutamate receptor 2/3 (mGluR2/3) ligands show efficacy in modulating the responses induced by activation of 5-HT2ARs. The formation of a 5-HT2AR-mGluR2 complex suggests a functional interaction that affects the hallucinogen-regulated cellular signaling pathways. Here, we tested the cellular and behavioral effects of hallucinogenic 5-HT2AR agonists in mGluR2 knockout (mGluR2-KO) mice. Mice were intraperitoneally injected with the hallucinogens DOI (2 mg/kg) and LSD (0.24 mg/kg), or vehicle. Head-twitch behavioral response, expression of c-fos, which is induced by all 5-HT2AR agonists, and expression of egr-2, which is hallucinogen-specific, were determined in wild type and mGluR2-KO mice. [(3)H]Ketanserin binding displacement curves by DOI were performed in mouse frontal cortex membrane preparations. Head twitch behavior was abolished in mGluR2-KO mice. The high-affinity binding site of DOI was undetected in mGluR2-KO mice. The hallucinogen DOI induced c-fos in both wild type and mGluR2-KO mice. However, the induction of egr-2 by DOI was eliminated in mGlu2-KO mice. These findings suggest that the 5-HT2AR-mGluR2 complex is necessary for the neuropsychological responses induced by hallucinogens.
Volume 493(3)
Pages 76-9
Published 2011-4-15
DOI 10.1016/j.neulet.2011.01.046
PII S0304-3940(11)00092-9
PMID 21276828
PMC PMC3064746
MeSH Animals Behavior, Animal / drug effects Behavior, Animal / physiology* Early Growth Response Protein 2 / biosynthesis Early Growth Response Protein 2 / physiology Frontal Lobe / drug effects Frontal Lobe / physiology Genes, fos / physiology Hallucinogens / metabolism* Hallucinogens / toxicity Male Mice Mice, 129 Strain Mice, Knockout Protein Binding / drug effects Protein Binding / physiology Receptor, Serotonin, 5-HT2A / deficiency Receptor, Serotonin, 5-HT2A / physiology* Receptors, Metabotropic Glutamate / metabolism* Schizophrenia / chemically induced Schizophrenia / metabolism Serotonin 5-HT2 Receptor Agonists / metabolism* Serotonin 5-HT2 Receptor Agonists / toxicity Signal Transduction / drug effects Signal Transduction / physiology
IF 2.274
Times Cited 118
Mice RBRC01351