Discriminative stimulus properties of nicotine: Approaches to evaluating potential nicotinic receptor agonists and antagonists

Abstract

The prototypic nicotinic acetylcholinergic receptor (nAChR) agonist, nicotine, is one of the primary psychoactive ingredients of tobacco. This review examines the effects of nicotine and similar compounds in nicotine discrimination procedures, a paradigm in which the subjective effects of nicotine can be modeled in animals. Results of these studies have shown that the discriminative stimulus effects of nicotine are shared by nicotine analogues and by the novel nicotinic agonists, epibatidine and ABT-418, and can be antagonized by the nAChR channel blocker, mecamylamine. Individual and strain differences in sensitivity to the discriminative stimulus effects of nicotine have been noted, suggesting the possibility of genetic differences in the functioning of nACh receptors or related processes. In human smokers, individual variability is also observed; however, the degree of within smoker (but between situation) variability far exceeds between smoker variability. Further research into the ways in which situational factors affect the discriminative stimulus effects of nicotine is needed. (C) 1996 Wiley-Liss, Inc