Chaudhri Nadia, Caggiula Anthony R, Donny Eric C, Palmatier Matthew I, Liu Xiu, Sved Alan F
Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Psychopharmacology (Berl). 2006 Mar;184(3-4):353-66. doi: 10.1007/s00213-005-0178-1. Epub 2005 Oct 21.
Although considerable progress has been made, we do not yet fully understand the behavioral and neurobiological basis of nicotine reinforcement, and without this knowledge, treatment strategies aimed at reducing smoking remain deficient.
This review describes an original perspective on nicotine reinforcement, which arises from substantial evidence of complex interactions between nicotine and nonpharmacological stimuli. We hypothesize that nicotine reinforcement derives from at least two sources: (1) primary reinforcement, an action that requires response-dependent drug administration and is capable of conveying secondary reinforcing effects on associated stimuli, and (2) the reinforcement-enhancing effect of nicotine, which directly enhances behavior maintained by salient nonnicotine stimuli and does not require a contingent relationship between drug administration and reinforced operant responding. Although novel for nicotine, this hypothesis has origins in an extensive literature on the reinforcing effects of psychostimulants. Empirical support for this hypothesis, based largely on animal models of reinforcement, will be presented.
Animal models of drug reinforcement have evolved to reflect our growing awareness of the multidimensional nature of drug dependence in humans. Investigating the interaction between nicotine and nonpharmacological stimuli within the context of the drug self-administration paradigm in rats has generated new insights into the paradox of how nicotine, an apparently weak primary reinforcer, can sustain the robust behavior observed in self-administration and in smoking. The hypothesis presented in this paper--that nicotine acts as both a primary reinforcer and an enhancer of other nonnicotine reinforcers--provides important direction for future investigations into the neurobiology of nicotine reinforcement and treatments for smoking cessation.
尽管已取得了显著进展，但我们尚未完全理解尼古丁强化作用的行为学和神经生物学基础。缺乏这方面的知识，旨在减少吸烟的治疗策略仍然存在不足。
本综述描述了一种关于尼古丁强化作用的独到观点，该观点源于尼古丁与非药物刺激之间复杂相互作用的大量证据。我们假设尼古丁强化作用至少源于两个方面：（1）初级强化，这是一种需要依赖反应给药的行为，并且能够对相关刺激产生次级强化作用；（2）尼古丁的强化增强作用，它直接增强由显著非尼古丁刺激维持的行为，并且不需要给药与强化操作反应之间存在偶然关系。尽管这一假设对于尼古丁来说是新颖的，但它起源于关于精神兴奋剂强化作用的大量文献。本文将主要基于强化作用的动物模型，展示对这一假设的实证支持。
药物强化作用的动物模型已经发展，以反映我们对人类药物依赖多维性质的日益认识。在大鼠药物自我给药范式的背景下，研究尼古丁与非药物刺激之间的相互作用，为理解尼古丁这一明显较弱的初级强化剂如何能维持在自我给药和吸烟中观察到的强烈行为这一悖论提供了新的见解。本文提出的假设——尼古丁既作为初级强化剂，又作为其他非尼古丁强化剂的增强剂——为未来尼古丁强化作用的神经生物学研究和戒烟治疗提供了重要方向。
