Adrenocortical hormone regulation of nicotine sensitivity in mice

The possibility that nicotine-induced corticosterone (CCS) release regulates nicotine sensitivity was investigated in female mice of the C3H strain. Adrenalectomy (ADX) resulted in an increase in nicotine sensitivity as measured in a number of physiological and behavioral tests. In ADX animals, chronic CCS (100 micrograms/ml) administered in the drinking solution normalized nicotine sensitivity. Dexamethasone (DEX), a potent synthetic glucocorticoid which interacts with a distinct population of CNS steroid receptors, did not reverse the effects of ADX. Unoperated animals administered CCS (200 micrograms/ml) were protected from the effects of nicotine for several test battery parameters. ADX had no effect on the number of brain nicotinic cholinergic receptors and also did not alter nicotine metabolism. These data support the hypothesis that CCS secretion modulates nicotine sensitivity in the mouse; however, the mechanisms by which this regulation occurs are unknown.