Group II metabotropic glutamate receptor modulation of DOI-induced c-fos mRNA and excitatory responses in the cerebral cortex.
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.
Zhai
Yan
Y
Lilly Research Laboratories, Neuroscience Research Division, Eli Lilly and Company, Lilly Corperate Center, Indianapolis, IN 46285, USA.
George
Carolyn A
CA
Zhai
Jin
J
Nisenbaum
Eric S
ES
Johnson
Michael P
MP
Nisenbaum
Laura K
LK
D000596:Amino Acids / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D018755:GABA Agonists / Q000494:pharmacology; D007090:Image Interpretation, Computer-Assisted; D017403:In Situ Hybridization; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014966:Xanthenes / Q000494:pharmacology
D000596:Amino Acids; D000662:Amphetamines; D001643:Bridged Bicyclo Compounds; D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; C114624:LY 341495; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D018094:Receptors, Metabotropic Glutamate; D017366:Serotonin Receptor Agonists; D014966:Xanthenes; C108822:metabotropic glutamate receptor 2; D004247:DNA; C104753:eglumetad; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine