Noradrenergic regulation of immediate early gene expression in rat forebrain: differential effects of αl- and α2-adrenoceptor drugs

Abstract

Noradrenergic (NAergic) transmission in the rat cerebral cortex has recently been shown to be involved in the regulation of the basal expression of NGFI-A, an immediate early gene (IEG) which encodes a zinc-finger transcription factor. The present study further investigated the role of the NAergic system in mediating cortical IEG expression and possible topographical changes in expression of NGFI-A mRNA in rat forebrain after alpha 1- and alpha 2-adrenoceptor (AR) agonist and antagonist treatment. Expression of c-fos and c-jun, which encode leucine-zipper class transcription factors, was also studied. Male Sprague-Dawley rats were injected intraperitoneally with either an alpha 1-AR agonist (methoxamine, 5 or 10 mg/kg); an alpha 1-AR antagonist (prazosin, 5 mg/kg); an alpha 2-AR agonist (clonidine, 0.5 mg/kg); or an alpha 2-AR antagonist (methoxyidazoxan, 5 mg/kg) and killed after 1 h. IEG mRNA levels were detected by quantitative in situ hybridization histochemistry using 35S-labelled oligonucleotides. High basal levels of NGFI-A mRNA were present in cortical layers IV and VI, hippocampal CA1, piriform cortex, amygdala and caudate putamen. alpha 1-AR agonist and antagonist treatment had essentially no effect on IEG mRNA, despite producing characteristic behavioral and peripheral effects at the doses used. Methoxyidazoxan significantly increased (mean%) NGFI-A mRNA in: cerebral cortex (44); caudate putamen (82); amygdala (92); and CA1 of hippocampus (48), while clonidine significantly decreased NGFI-A mRNA in the various cortical layers to a similar extent (27-37%). Basal c-fos mRNA expression was lower than that for NGFI-A in forebrain areas including cortex, caudate putamen and hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS)