Chronic corticosterone administration modulates nicotine sensitivity and brain nicotinic receptor binding in C3H mice

Glucocorticoid regulation of nicotine sensitivity was investigated in adrenalectomized (ADX) and sham-operated C3H mice administered chronic corticosterone (CCS) replacement therapy. Hormone pellets (60% CCS or pure cholesterol) were implanted at the time of surgery and animals were tested for nicotine sensitivity in a battery of behavioral and physiological tests. ADX-induced increases in nicotine sensitivity were reversed by chronic CCS replacement. Sham-operated animals that received CCS supplementation were subsensitive to the effects of nicotine. In both ADX and sham-operated animals, chronic CCS administration induced a decrease in the number of CNS nicotinic cholinergic receptors labeled by alpha-[125I]-bungarotoxin. Binding was decreased by 30-60% depending on brain region; no changes in affinity (KD) were detected. The number of brain nicotinic sites labeled by [3H]-nicotine was unaltered following 1 week of chronic CCS administration. These data support the hypothesis that glucocorticoids modulate nicotine sensitivity in the C3H mouse. In animals chronically treated with CCS, nicotine tolerance may be due to CCS-induced changes in nicotinic cholinergic receptor binding or the presence of high CCS titers at the time of testing.