期刊
NEUROPHARMACOLOGY
卷 46, 期 3, 页码 331-339出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2003.09.017
关键词
5-HT2A receptors; Arc; c-fos; immediate early gene; glutamate; AMPA; NMDA
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-HT2A 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-HT2 agonist DOI induced a marked increase in expression of Are mRNA in a variety of cortical regions. This effect was blocked by the selective 5-HT2A receptor antagonist, MDL 100,907, but not the 5-HT2B/2C receptor antagonist, SB206553. The AMPA receptor antagonist GYKI 52466 also attenuated DOI-induced Are 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-HT2A 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-HT2A receptor-induced Arc expression. This finding, together with evidence of extensive Arc and c-fos co-localisation, suggests that 5-HT2A receptor activation may induce the expression of both effector and transcription factor IEGs via common molecular and cellular substrates. (C) 2003 Elsevier Ltd. All rights reserved.
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