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

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Moreno, José L., Holloway, Terrell, Albizu, Laura, Sealfon, Stuart C., González-Maeso, Javier·2011·Neuroscience Letters

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. [3H]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.

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Metadata

Authors
Moreno, J. L., Holloway, T., Albizu, L., Sealfon, S. C., & González-Maeso, J.
Venue
Neuroscience Letters
Publisher
Elsevier BV
Published
2011-04
Volume
493
Issue
3
Pages
76-79
ISSN
0304-3940 (ISSN-L)
OpenAlex
W2089436854
Cited by
234
References
4
FWCI
17.84
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists. https://app.cochat.ai/papers/10.1016/j.neulet.2011.01.046
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Moreno, J. L., Holloway, T., Albizu, L., Sealfon, S. C., & González-Maeso, J. (2011). Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists. Neuroscience Letters. https://doi.org/10.1016/j.neulet.2011.01.046

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