Nicotine as a discriminative stimulus: a neurobehavioral approach to studying central cholinergic mechanisms

A major goal of basic nicotine research is to obtain information useful to the clinician in determining why and how people become dependent on this substance via the use of tobacco products. To accomplish this, the basic scientist must first develop an animal model of nicotine action that is parallel to its effects in humans. This review describes such a model, based on the ability of nicotine to exert discriminative stimulus (DS) control over behavior. The nicotine DS, as studied in the rat, mouse, or subhuman primate, appears to provide information analogous to human subjective reports concerning the effects of smoking. Findings indicate that nicotine is specific and selective in its actions, explaining, in part, why tobacco is dependence-producing. The nicotine DS effect is stereoselective and appears to be the result of an action at specific central nicotinic cholinergic (N-Ch) receptors located in at least two brain areas, the hippocampus and midbrain reticular formation. Whether acetylcholine is the mediator of nicotine's effects at these receptor sites, as was once thought, has yet to be clearly determined. Finally, these N-Ch receptors appear to have a wide distribution and may also sit on presynaptic dopamine neurons, helping to explain some of nicotine's additional behavioral and/or rewarding effects.