Concerns about body weight represent an important barrier to public health efforts aimed at reducing smoking. Epidemiological studies have found that current smokers weigh less than non-smokers, smoking cessation results in weight gain, and weight restriction is commonly cited as a reason for smoking. The mechanisms underlying the relationship between smoking and weight are complex and may involve a number of factors including changes in caloric intake, physical activity, metabolic rate, and lipogenesis. Amongst these possible mechanisms, nicotine-induced enhancement of food reinforcement may be particularly important. In this paper, we first review data from our laboratory that highlight two distinct ways in which nicotine impacts reinforced behavior: 1) by acting as a primary reinforcer; 2) by directly (non-associatively) enhancing the reinforcing effects of other stimuli. We then elaborate on the reinforcement-enhancing effects of nicotine as they pertain to behaviors and stimuli related to food. Data from both laboratory animals and humans support the assertion that nicotine enhances the reinforcing efficacy of food and suggest that the influence of these effects on eating may be most important after nicotine cessation when nicotine’s effects on satiety subside. Finally, we discuss the theoretical and clinical implications of this perspective for understanding and addressing the apparent tradeoff between smoking and weight gain. Better understanding of the mechanisms underlying the reinforcement-enhancing effects of nicotine broadly, and the effects on food reinforcement per se, may aid in the development of new treatments with better long term outcomes.

Introduction: The Family Smoking Prevention and Tobacco Control Act in the United States and the World Health Organization Framework Convention on Tobacco or Health ratified by over 170 countries render scientific investigations into the abuse liability, harm, and effects of tobacco more critical than ever. A key area to explore relates to the potential regulation of nicotine content in cigarettes. Determining the nicotine content per cigarette below which smokers reliably reduce their consumption of and dependence on cigarettes, an idea proposed almost 20 years ago (Benowitz & Henningfield, 1994), could be a powerful approach to reduce the abuse liability and consequent harm from cigarettes. However, this approach is laden with potentially complex issues. Many of these complications can be studied using animal models, but they require a particular perspective.

introduction: Food and Drug Administration-mandated product standards that drastically reduce nicotine content in cigarettes aim to decrease smoking and thus improve health outcomes for millions of U.S. smokers. Researchers have suggested that nicotine reduction should be implemented gradually, but a gradual nicotine reduction may shift the minimum level of nicotine required to reinforce behavior or may result in different levels of compensatory smoking behavior.

The results of these studies support the assertion that the therapeutic efficacy of VAR may be due to the partial agonist characteristics of the drug, specifically, its ability to partially replace the reinforcement-enhancing effects of NIC as well as antagonize these effects.

Rationale-Nicotine serves as a primary reinforcer but also potently enhances responding for nonnicotine stimuli with reinforcing properties. One of the most successful pharmacotherapies for smoking cessation, bupropion, also increases responding for non-drug reinforcers such as food and brain stimulation rewards.Objective-The present studies investigated whether treatment with bupropion and nicotine had similar effects on responding for a reinforcing visual stimulus (VS). They also investigated whether the effects of bupropion and nicotine depended on common pharmacological substrates.Results-Nicotine (0.4 mg/kg base) enhanced responding for the VS and this enhancing effect increased across testing sessions, replicating our previous findings. Bupropion (3, 10, and 30 mg/kg salt) dose-dependently increased responding for the VS. Treatment with 10 and 30 mg/kg bupropion resulted in a profile similar to nicotine; operant responding increased over repeated drug treatments. The reinforcement enhancing effect of nicotine, but not bupropion, was blocked by pretreatment with the nicotinic acetylcholine receptor antagonist mecamylamine. In contrast, the reinforcement enhancing effect of bupropion, but not nicotine, was blocked by pretreatment with the alpha noradrenergic antagonist prazosin. Conclusion-The reinforcement enhancing effects of nicotine and bupropion increased over time and repeated treatments suggesting a shared mechanism of action. However, the reinforcement enhancing effects of nicotine are mediated by nicotinic acetylcholine receptors, whereas the reinforcement enhancing effects of bupropion were mediated by alpha noradrenergic receptors.