Group II metabotropic glutamate receptor modulation of DOI-induced c-fos mRNA and excitatory responses in the cerebral cortex

Neuropsychopharmacology. 2003 Jan;28(1):45-52. doi: 10.1038/sj.npp.1300013.


Recent studies have demonstrated that the hallucinogen 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) enhances glutamatergic transmission in the prefrontal cortex. This increase can be suppressed by metabotropic glutamate2/3 (mGlu2/3) receptor activation. In addition to enhancing glutamatergic transmission, DOI increases cortical c-fos expression. We tested if a reduction in glutamate release produced by mGlu2/3 receptor activation attenuates DOI-induced c-fos expression in the cortex. Similar to previous studies, DOI produced a robust increase in c-fos mRNA throughout the cortex, including the prefrontal, frontoparietal, and somatosensory regions. Pretreatment with the mGlu2/3 agonist LY379268 attenuated the DOI-induced increase in the prefrontal cortex. This suppression was blocked by the mGlu2/3 antagonist LY341495. In contrast, the DOI-induced increase in c-fos mRNA in the frontoparietal and somatosensory cortex was unaffected by the mGlu2/3 agents. These findings suggest that Group II metabotropic glutamate receptor agonists are capable of modulating postsynaptic function preferentially in the limbic cortex under conditions of enhanced glutamate release.

MeSH terms

  • Amino Acids / pharmacology
  • Amphetamines / pharmacology*
  • Animals
  • Autoradiography
  • Bridged Bicyclo Compounds / pharmacology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism*
  • DNA / biosynthesis
  • DNA / genetics
  • Electrophysiology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects*
  • GABA Agonists / pharmacology
  • Image Interpretation, Computer-Assisted
  • In Situ Hybridization
  • Male
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism
  • Proto-Oncogene Proteins c-fos / biosynthesis*
  • RNA, Messenger / biosynthesis*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Metabotropic Glutamate / drug effects
  • Receptors, Metabotropic Glutamate / metabolism*
  • Serotonin Receptor Agonists / pharmacology*
  • Xanthenes / pharmacology


  • Amino Acids
  • Amphetamines
  • Bridged Bicyclo Compounds
  • Excitatory Amino Acid Antagonists
  • GABA Agonists
  • LY 341495
  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Receptors, Metabotropic Glutamate
  • Serotonin Receptor Agonists
  • Xanthenes
  • metabotropic glutamate receptor 2
  • DNA
  • eglumetad
  • 4-iodo-2,5-dimethoxyphenylisopropylamine