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
Arc 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-HT(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-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.