Group II metabotropic glutamate receptor modulation of doi-induced c-fos mRNA and excitatory responses in thecerebral cortex

Abstract

Recent studies have demonstrated that the hallucinogen l-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) enhances glutamatergic transmission in the prefrontalcortex. This increase can be suppressed by metabotropic glutamate2/3 (mGlu2/3) receptoractivation. In addition to enhancing glutamatergic transmission, DOI increases corticalc-fos expression. We tested if a reduction inglutamate release produced by mGlu2/3 receptor activation attenuates DOI-inducedc-fosexpression in the cortex. Similarto previousstudies, DOI produced a robust increase inc-fosmRNA throughout the cortex, including the prefrontal, frontoparietal, andsomatosensory regions. Pretreatment with the mGlu2/3 agonist LY379268 attenuated the DOI-induced increase in the prefrontalcortex. This suppression was blocked by the mGlu2/3 antagonist LY341495. In contrast, the DOI-induced increase inc-fosmRNA in thefrontoparietal and somatosensory cortex was unaffected by the mGlu2/3 agents. These findings suggest that Group II metabotropicglutamate receptor agonists are capable of modulating postsynaptic function preferentially in the limbic cortex under conditions ofenhanced glutamate release. © 2003 American College of Neuropsychopharmacology.