The regulation of hippocampal nicotinic acetylcholine receptors (nAChRs) after a protracted treatment with selective or nonselective nAChR agonists

In rats, 1 mg/kg twice daily for 10 d of nicotine, a nonselective agonist o f nicotinic acetylcholine receptors (nAChRs), fails to change alpha(4) acid beta(2) nAChR subunit mRNA but significantly decreased alpha(7) nAChR subu nit mRNA and protein expression, which is associated with a 35-40% decrease in the number of I-125-alpha-Bgtx binding sites in hippocampus. In additio n, this schedule of nicotine treatment produced a 40% increase in the numbe r of high- (K-D 1 nM), but decreased by 25% the number of low-affinity (K-D 30 nM) binding sites for H-3-epibatidine in hippocampus. In contrast, repe ated treatment with lobeline (2.7 mg/kg twice daily for 10 d), which select ively binds to high-affinity binding nAChRs, fails to change the expression of high- or low-affinity nAChRs. These data suggest that a simultaneous up regulation of high-affinity nAChRs and downregulation of low-affinity nAChR s is elicited by ligands that can bind to both low- and high-affinity nAChR s, but not by selective agonists of high-affinity nAChRs. One might infer t hat in hippocampus, high- and low-affinity nAChRs may be located in the sam e cells. When these two receptor types are stimulated simultaneously by non selective ligands for high- and low-affinity nAChRs, they interact, bringin g about an increase in binding site density of the high-affinity nAChRs.