AN AUTORADIOGRAPHIC ANALYSIS OF ALTERATIONS IN NICOTINIC CHOLINERGIC RECEPTORS FOLLOWING 1 WEEK OF CORTICOSTERONE SUPPLEMENTATION

Previous studies from our laboratory have established an interaction between central nervous system nicotinic cholinergic systems and glucocorticoid hormones. When mice are treated for 1 week with exogenous corticosterone (CORT) they become insensitive to the behavioral and physiological actions of nicotine and also have a reduction in brain alpha-bungarotoxin (BTX) receptor binding. In the present study, mice were treated with high stress levels of CORT and nicotinic receptor binding was measured using quantitative auto-radiographic methods. L-[H-3]-nicotine and alpha-[I-125]-bungarotoxin were used to label both high- and low-affinity nicotinic sites. Chronic CORT administration reduced BTX binding in 77 of 115 (67.0%) brain regions examined. In general, forebrain regions were more sensitive to this regulation than were more posterior brain regions. Hippocampal and hypothalamic regions were particularly susceptible, with binding in treated animals being reduced by up to 80% in some nuclei. L-[H-3]-nicotine sites were not as sensitive to CORT regulation as binding was significantly reduced in only 7 of the 83 (8.4%) regions measured. Regions affected were restricted to the thalamus and septum. The mechanism by which CORT reduces brain nicotinic cholinergic receptor binding is unknown and may or may not be dependent on CNS glucocorticoid receptors.