Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists

NEUROSCIENCE LETTERS

卷:493

Article

Moreno, Jose L.¹  Holloway, Terrell¹  Albizu, Laura²  Sealfon, Stuart C.^2,4  Gonzalez-Maeso, Javier^1,2,3 

[1] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA

[2] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA

[3] Mt Sinai Sch Med, Friedman Brain Inst, New York, NY 10029 USA

[4] Mt Sinai Sch Med, Ctr Translat Syst Biol, New York, NY 10029 USA

关键词: Hallucinogenic drugs;    LSD;    Serotonin 5-HT2A receptor;    Metabotropic glutamate mGlu2 receptor;    G protein-coupled receptor (GPCR);    Schizophrenia and psychosis;   

DOI  :  10.1016/j.neulet.2011.01.046

来源: Elsevier

【 摘 要 】

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. [H-3]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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

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