THE ROLE OF CORTICOSTEROIDS IN NICOTINES PHYSIOLOGICAL AND BEHAVIORAL-EFFECTS

This paper reviews evidence indicating that adrenal corticosteroids mo dulate the responsiveness of mice and rats to nicotine. Adrenalectomy increases, and both acute and chronic corticosteroid administration de crease, some of the physiological and behavioral effects of nicotine. One function of adrenal steroids may be to regulate stress-induced cha nges in nicotine sensitivity. Another is to mediate the development of chronic tolerance when nicotine is given intermittently, and when the resulting tolerance has a learned component. A role of glucocorticoid s in the development of tolerance to nicotine is suggested by the find ings that a conditioned elevation of plasma corticosterone, which anti cipates nicotine delivery, accompanies the development of chronic tole rance and that environmental cues evoke a conditioned corticosterone r esponse, but only after they have become associated with nicotine deli very. The mechanisms by which adrenal steroids modulate nicotine sensi tivity are not known, although recent in vitro evidence suggests that steroids can rapidly and reversibly reduce nicotinic receptor function . While most of the data are consistent with the hypothesis that corti costeroids reduce nicotine responsiveness, and thus promote a learned form of tolerance, there are new findings that corticosteroids increas e the development of sensitization to the locomotor-activating effects of nicotine. These data suggest that formulations postulating a unidi rectional effect of corticosteroids on nicotine's actions (e.g. decrea sed sensitivity) must be revised to take into account interacting vari ables such as the specific nicotine effect being studied and whether t hat effect normally exhibits tolerance or sensitization. Finally, rese arch is presented which indicates that the corticosterone-elevating ef fects of nicotine, previously reported for experimenter-administered d rug, are also produced when nicotine administration is contingent on a n operant response, and at a dose which sustains the development of ni cotine self-administration in rats. These findings highlight the feasi bility of using self-administration models in future explorations of t he relationship between adrenal steroids and nicotine function. (C) 19 98 Elsevier Science Ltd. All rights reserved.