Caggiula A R, Donny E C, White A R, Chaudhri N, Booth S, Gharib M A, Hoffman A, Perkins K A, Sved A F
Department of Psychology, 455 Langley Hall, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Pharmacol Biochem Behav. 2001 Dec;70(4):515-30. doi: 10.1016/s0091-3057(01)00676-1.
A paradox exists regarding the reinforcing properties of nicotine. The abuse liability associated with smoking equals or exceeds that of other addictive drugs, yet the euphoric, reinforcing and other psychological effects of nicotine, compared to these other drugs, are more subtle, are manifest under more restricted conditions, and do not readily predict the difficulty most smokers experience in achieving abstinence. One possible resolution to this apparent inconsistency is that environmental cues associated with drug delivery become conditioned reinforcers and take on powerful incentive properties that are critically important for sustaining smoking in humans and nicotine self-administration in animals. We tested this hypothesis by using a widely employed self-administration paradigm in which rats press a lever at high rates for 1 h/day to obtain intravenous infusions of nicotine that are paired with two types of visual stimuli: a chamber light that when turned on signals drug availability and a 1-s cue light that signals drug delivery. We show that these visual cues are at least as important as nicotine in sustaining a high rate of responding once self-administration has been established, in the degree to which withdrawing nicotine extinguishes the behavior, and in the reinstatement of lever pressing after extinction. Additional studies demonstrated that the importance of these cues was manifest under both fixed ratio and progressive ratio (PR) schedules of reinforcement. The possibility that nicotine-paired cues are as important as nicotine in smoking behavior should refocus our attention on the psychology and neurobiology of conditioned reinforcers in order to stimulate the development of more effective treatment programs for smoking cessation.
关于尼古丁的强化特性存在一个悖论。与吸烟相关的滥用倾向等于或超过其他成瘾性药物，但与这些其他药物相比，尼古丁的欣快感、强化作用及其他心理效应更为微妙，在更有限的条件下才会显现，并且不容易预测大多数吸烟者在戒烟时所经历的困难。对于这种明显的不一致，一种可能的解释是，与药物递送相关的环境线索成为条件性强化物，并具有强大的激励特性，这对于维持人类吸烟和动物自我给药尼古丁至关重要。我们通过使用一种广泛采用的自我给药范式来检验这一假设，在该范式中，大鼠每天以高频率按压杠杆1小时，以获得静脉注射的尼古丁，同时伴有两种视觉刺激：一种是打开时表示有药物可用的舱内灯光，另一种是表示药物递送的1秒提示灯光。我们发现，一旦建立了自我给药行为，这些视觉线索在维持高反应率、尼古丁戒断使行为消退的程度以及消退后杠杆按压行为的恢复方面至少与尼古丁同样重要。额外的研究表明，这些线索的重要性在固定比率和累进比率（PR）强化程序下均有体现。尼古丁配对线索在吸烟行为中与尼古丁同样重要，这一可能性应使我们将注意力重新集中在条件性强化物的心理学和神经生物学上，以促进开发更有效的戒烟治疗方案。
