Studies of 5-HT-glutamate interactions suggest that activation of brain 5-HT(2A) receptors leads to an
AMPA receptor-mediated induction of the immediate early (activity-dependent) gene,
Arc (Arg3.1). In this respect,
noradrenaline-
glutamate interactions are poorly characterised. Here we investigated the influence on regional brain
Arc gene expression of selective blockade of α(2)-adrenoceptors in rats. Several complementary techniques were used: qPCR (
mRNA, discrete tissue punches), in situ hybridisation (
mRNA, sections) and immunocytochemistry. The α(2)-adrenoceptor antagonist,
RX 821002, dose-dependently and time-dependently (maximal effect 2 h) increased
Arc mRNA levels as demonstrated both by qPCR and in situ hybridisation. The α(2)-adrenoceptor antagonist,
atipamezole, also increased
Arc mRNA in in situ hybridisation studies. Changes in
Arc mRNA after
RX 821002 were of similar magnitude in punches and intact tissue sections and region-specific, with effects being most pronounced in parietal cortex and caudate putamen, less robust in frontal cortex, and not detectable in hippocampal sub-regions. Both qPCR and in situ hybridisation studies demonstrated that RX 821002-induced
Arc mRNA was blocked by the
AMPA antagonist,
GYKI 52466. Pretreatment with the
NMDA antagonist
MK 801 also prevented RX 821002-induced
Arc mRNA, as did the mGluR5 antagonist MPEP, whilst the
mGluR2/3 antagonist,
LY341495, had no effect. Finally, immunocytochemical studies showed that
RX 821002 increased
Arc-immunoreactivity in cells in close apposition to α(2)-adrenoceptor-positive processes. Thus, employing three complementary techniques, these observations demonstrate that blockade of α(2)-adrenoceptors triggers brain expression of the immediate early gene,
Arc, and that this effect involves the recruitment of
AMPA,
NMDA and mGluR5 but not
mGluR2/3 glutamatergic receptors.