Caggiula Anthony R, Donny Eric C, Palmatier Matthew I, Liu Xiu, Chaudhri Nadia, Sved Alan F
Department of Psychology, 3131 Sennott Square, 210 South Bouquet Street, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Nebr Symp Motiv. 2009;55:91-109. doi: 10.1007/978-0-387-78748-0_6.
Models of intravenous nicotine self-administration in laboratory animals are being used to investigate the behavioral and neurobiological consequences of nicotine reinforcement, and to aid in the development of novel pharmacotherapies for smoking cessation. Central to these models is the principle of primary reinforcement, which posits that response-contingent presentation of a primary reinforcer, nicotine, engenders robust operant behavior, whereas response-independent drug delivery does not. This dictum of nicotine as a primary reinforcer has been widely used to explain why people smoke tobacco-smoking results in the rapid delivery of nicotine to the brain, setting up a cascade of neurobiological processes that strengthen subsequent smoking behavior. However, there is mounting evidence that the primary reinforcement model of nicotine self-administration fails to fully explain existing data from both the animal self-administration and human smoking literatures. We have recently proposed a "dual reinforcement" model to more fully capture the relationship between nicotine and self-administration, including smoking. Briefly, the "dual reinforcement" model posits that nicotine acts as both a primary reinforcer and a reinforcement enhancer. The latter action of nicotine had originally been uncovered by showing that a reinforcing VS, which accompanies nicotine delivery, synergizes with nicotine in the acquisition and maintenance of self-administration, and that this synergism can be reproduced by combining operant responding for the reinforcing stimulus with non-contingent (response-independent) nicotine. Thus, self-administration (and smoking) is sustained by three actions: (1) nicotine, acting as a primary reinforcer, can sustain behavior that leads to its delivery; (2) nicotine, acting as a primary reinforcer, can establish neutral environmental stimuli as conditioned reinforcers through Pavlovian associations; and (3) nicotine, acting as a reinforcement enhancer, can magnify the incentive value of accompanying stimuli, be they conditioned or unconditioned reinforcers.
实验室动物静脉注射尼古丁自我给药模型正被用于研究尼古丁强化的行为和神经生物学后果，并有助于开发戒烟的新型药物疗法。这些模型的核心是初级强化原则，该原则认为，初级强化物尼古丁的反应性呈现会产生强烈的操作性行为，而与反应无关的药物递送则不会。尼古丁作为初级强化物的这一准则已被广泛用于解释人们吸烟的原因——吸烟会导致尼古丁迅速输送到大脑，引发一系列神经生物学过程，从而强化后续的吸烟行为。然而，越来越多的证据表明，尼古丁自我给药的初级强化模型无法完全解释动物自我给药和人类吸烟文献中的现有数据。我们最近提出了一种“双重强化”模型，以更全面地描述尼古丁与自我给药（包括吸烟）之间的关系。简而言之，“双重强化”模型认为，尼古丁既作为初级强化物，又作为强化增强剂。尼古丁的后一种作用最初是通过以下方式发现的：与尼古丁递送相伴的强化性VS在自我给药的获得和维持中与尼古丁协同作用，并且这种协同作用可以通过将对强化刺激的操作性反应与非偶然性（与反应无关）尼古丁相结合来重现。因此，自我给药（和吸烟）由三种作用维持：（1）尼古丁作为初级强化物，可以维持导致其递送的行为；（2）尼古丁作为初级强化物，可以通过巴甫洛夫式关联将中性环境刺激确立为条件强化物；（3）尼古丁作为强化增强剂，可以放大伴随刺激的激励价值，无论这些刺激是条件强化物还是非条件强化物。
