Effects of 6-cyano-7-nitroquinoxaline-2,3-dione on nicotinic receptor subunit transcript expression in the rat brain

Abstract

The nicotinic cholinergic system exerts potent modulatory effects on glutamatergic neurotransmission, an effect mediated in part by increased glutamate release following activation of presynaptic nicotinic cholinergic receptors. Ionotropic glutamate receptor agonists also stimulate release of acetylcholine, suggesting that these neurotransmitter systems reciprocally regulate one another. We investigated an interface between the nicotinic cholinergic and glutamatergic systems by measuring nicotinic receptor subunit transcript expression following administration of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an antagonist of the AMPA and kainate subtypes of glutamate receptors. Using [ 35 S] in situ hybridization, we measured expression of Α2, Α3, Α4, Α5, Α7, Β2, Β3, and Β4 nicotinic receptor subunit transcripts in the rat forebrain. Following 7 days of treatment with vehicle or CNQX (1 mg/kg/day or 10 mg/kg/day), changes in nicotinic receptor subunit transcript expression were restricted to subunits that form heteromeric receptors. We found increased levels of transcripts for Α2 and Β2 nicotinic receptor subunits in the hippocampus, decreased Α4 subunit transcripts in the medial habenula and amygdala, and increased Β2 subunit transcripts in the septum and piriform cortex. We did not detect changes in expression of transcripts for the Α7 subunit, which forms homomeric nicotinic receptors. Our findings indicate that expression of nicotinic cholinergic receptor subunit transcripts are regulated in a subunit- and region-specific fashion by CNQX, an antagonist of non-NMDA ionotropic glutamate receptors. Synapse 52:62–72, 2004. © 2004 Wiley-Liss, Inc.