Glutamate receptor activation is involved in 5-HT sub(2) agonist-induced Arc gene expression in the rat cortex

• Published in: Neuropharmacology 2004-03, Vol.46 (3), p.331-339
• Main Authors: Pei, Q, Tordera, R, Sprakes, M, Sharp, T
• Format: Article
• Language: English
• ISSN: 0028-3908
• DOI: 10.1016/j.neuropharm.2003.09.017

Brain 5-HT regulates the expression of gene transcription factor as well as novel effector immediate early genes (IEGs). The 5-HT regulation of the gene transcription factor IEG, c-fos, involves activation of 5-HT sub(2A) and ionotropic glutamate receptors. Here, we investigate whether these receptors are also involved in the regulation of the effector IEG, Arc. In rats, the 5- HT sub(2) agonist DOI induced a marked increase in expression of Arc mRNA in a variety of cortical regions. This effect was blocked by the selective 5-HT sub(2A) receptor antagonist, MDL 100, 907, but not the 5-HT sub(2B/2C) receptor antagonist, SB206553. The AMPA receptor antagonist GYKI 52466 also attenuated DOI-induced Arc mRNA expression, as did the NMDA receptor antagonist MK801 in some regions. Immunofluorescence studies showed that DOI increased Arc- immunoreactivity in cortical cells that expressed AMPA and NMDA receptor subunits but not the 5-HT sub(2A) receptor. Finally, DOI-induced Arc- immunoreactivity in cortical cells was extensively co-localised with c-fos- immunoreactivity. These results suggest that, as with c-fos expression, ionotropic glutamate receptors (AMPA and NMDA) are involved in 5-HT sub(2A) receptor-induced Arc expression. This finding, together with evidence of extensive Arc and c-fos co-localisation, suggests that 5-HT sub(2A) receptor activation may induce the expression of both effector and transcription factor IEGs via common molecular and cellular substrates.