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

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 alpha 2, alpha 3, alpha 4, alpha 5, alpha 7, beta 2, beta 3, and beta 4 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 alpha 2 and beta 2 nicotinic receptor subunits in the hippocampus, decreased alpha 4 subunit transcripts in the medial habenula and amygdala, and increased beta 2 subunit transcripts in the septum and piriform cortex. We did not detect changes in expression of transcripts for the alpha 7 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.