Behavioral evidence for interactions between a hallucinogenic drug and group II metabotropic glutamate receptors

Jonathan C. Gewirtz, Gerard J. Marek

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155 Scopus citations


Recent electrophysiological studies in our laboratory have demonstrated a physiological interaction between 5-HT(2A) and metabotropic glutamate 2/3 (mGlu2/3) receptors in the medial prefrontal cortex. Several behavioral studies have found that phenethylamine hallucinogens with partial agonist activity at 5-HT(2A) receptors induce head shakes when directly administered into the medial prefrontal cortex. The purpose of the present experiments was to examine whether an interaction occurs between mGlu2/3 and 5-HT(2A) receptors on a behavioral level using head shakes induced by phenethylamine hallucinogens as a model of 5-HT(2A) receptor activation. Administration of the mGlu2/3 agonist LY354740 (0.3-10 mg/kg, ip) suppressed head shakes induced by the phenethylamine hallucinogen 1-(2,5-dimethoxy-4-iodophenyl)-2- aminopropane (DOI). Conversely, administration of the mGlu2/3 antagonist LY341495 (1 mg/kg, ip) enhanced the frequency of DOI-induced head shakes. Taken together, these results raise the possibility that the psychomimetic properties of hallucinogenic drugs may be mediated in part, via increased glutamate release following activation of 5-HT(2A) receptors. (C) 2000 American College of Neuropsychopharmacology.

Original languageEnglish (US)
Pages (from-to)569-576
Number of pages8
Issue number5
StatePublished - Nov 2000

Bibliographical note

Funding Information:
Supported by PHS Grants K08 MH01551, a NARSAD Young Investigator Award (1999 Fairfax Investigator Award), and the State of Connecticut (G.J.M.). We thank Drs. Darryle Schoepp and James Monn for valuable discussions. We appreciate Dr. Younglim Lee's review of this manuscript. We thank Nigel Henry, Sara Heron, Andrew Kwak, Megan Lennon, and Boting Zhang for technical assistance. We also thank Leslie Rosello for secretarial assistance.


  • 5-HT(2A) receptors
  • DOI
  • Hallucinogens
  • Head shakes
  • LY354740
  • Phenethylamines
  • Serotonin
  • mGlu2/3 receptors


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