Rosecrans J A
Department of Pharmacology and Toxicology, School of Basic Health Sciences, Virginia Commonwealth University, Richmond 23298, USA.
J Subst Abuse. 1989;1(3):287-300.
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.
基础尼古丁研究的一个主要目标是获取对临床医生有用的信息，以确定人们为何以及如何通过使用烟草制品而对这种物质产生依赖。为实现这一目标，基础科学家必须首先建立一个与尼古丁在人类身上的作用效果相似的动物模型。本综述描述了这样一个模型，该模型基于尼古丁对行为施加辨别性刺激（DS）控制的能力。在大鼠、小鼠或非人灵长类动物中研究的尼古丁辨别性刺激，似乎能提供与人类关于吸烟效果的主观报告类似的信息。研究结果表明，尼古丁的作用具有特异性和选择性，这在一定程度上解释了烟草为何会导致成瘾。尼古丁辨别性刺激效应具有立体选择性，似乎是作用于至少两个脑区（海马体和中脑网状结构）中特定的中枢烟碱型胆碱能（N-Ch）受体的结果。乙酰胆碱是否如曾经所认为的那样是尼古丁在这些受体位点发挥作用的介质，还有待明确确定。最后，这些N-Ch受体似乎分布广泛，也可能存在于突触前多巴胺神经元上，这有助于解释尼古丁的一些其他行为和/或奖赏效应。
