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

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

Research output: Contribution to journalArticlepeer-review

166 Scopus citations

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 (2mg/kg) and LSD (0.24mg/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.

Original languageEnglish
Pages (from-to)76-79
Number of pages4
JournalNeuroscience Letters
Volume493
Issue number3
DOIs
StatePublished - 15 Apr 2011

Keywords

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

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