Modulation of DOI-induced increases in cortical BDNF expression by group II mGlu receptors

Jonathan C. Gewirtz, Andrew C. Chen, Rose Terwilliger, Ronald C. Duman, Gerard J. Marek

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

Previous studies have shown that 5-hydroxytryptamine2A (5-HT2A) receptor activation induces changes in the pattern of brain-derived neurotrophic factor (BDNF) mRNA expression in the neocortex and hippocampus, and that 5-HT2A receptor blockade interferes with the induction of BDNF mRNA by stress. Recent studies have also shown that activation of metabotropic glutamate group II (mGlu2/3) receptors suppresses 5-HT2A receptor-stimulated excitatory postsynaptic potentials/currents (EPSP/Cs) in pyramidal neurons in medial prefrontal cortex. Conversely, blockade of mGlu2/3 receptors enhances 5-HT-induced EPSCs. The current study examined the effects of the highly selective mGlu2/3 agonist (1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate monohydrate (LY354740) and the mGlu2/3 antagonist 2S-2-amino-2-(1S,2S-2-carboxycycloprop-1-yl)-3(xanthy-9-yl)propanoic acid (LY341495) on BDNF mRNA expression in medial prefrontal cortex induced by the hallucinogen and 5-HT2A/2B/2C agonist 1-(2,5-dimethoxy-4-iodophenethyl)-2-aminopropane (DOI). LY354740 (0.1-10 mg/kg) dose-dependently suppressed DOI-induced BDNF mRNA levels in medial prefrontal cortex. In contrast, the mGlu2/3 antagonist LY341495 (1 mg/kg) enhanced DOI-induced BDNF mRNA levels. BDNF mRNA expression was not altered by administration of the mGlu agonist or the antagonist alone. These results are discussed with respect to a potential role for group II mGlu agonists in the treatment of depression and schizophrenia.

Original languageEnglish (US)
Pages (from-to)317-326
Number of pages10
JournalPharmacology Biochemistry and Behavior
Volume73
Issue number2
DOIs
StatePublished - 2002

Bibliographical note

Funding Information:
Supported by PHS Grants K08 MH01551 (GJM), R01 MH62186 (GJM), R01 MH45481 (RSD), P01 MH25642 (RSD), a National Alliance for Research on Schizophrenia and Affective Disorders (NARSAD) Young Investigator Award (GJM), a Veterans Administration National Center Grant for PTSD (RSD) and the State of Connecticut. We also thank Drs. Darryle D. Schoepp and James Monn of Eli Lilly for generously supplying LY354740 and LY341495. We thank Allyson Abo for technical assistance and Leslie Rosello for secretarial assistance.

Keywords

  • 5-HT receptor
  • 5-Hydroxytryptamine receptor
  • Brain-derived neurotrophic factor
  • Glutamate
  • Hallucinogenic drugs
  • Medial prefrontal cortex
  • Metabotropic glutamate2/3 receptors
  • Phenethylamine hallucinogens
  • Serotonin
  • mGlu2 receptors

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