Varenicline rescues nicotine-induced decrease in motivation for sucrose reinforcement.

Varenicline is one of the top medications used for smoking cessation and is often prescribed before termination of nicotine use. The effect of this combined nicotine and varenicline use on the reward system and motivation for primary reinforcement is underexplored. The goal of this study was to assess the effects of nicotine and varenicline on motivation for a food reinforcer. In Experiment 1, we first assessed the responding for sucrose after pretreatment with nicotine (0, 0.1, or 0.4 mg/kg) and varenicline (0.0, 0.1, 1.0 mg/kg) using a behavioral economics approach. The responding for sucrose was then assessed using a progressive ratio schedule of reinforcement after pretreatment with all possible combinations of nicotine and varenicline doses. In Experiment 2, rats were assessed for the consumption of sucrose in home cages after pretreatment with nicotine and varenicline. We found that (a) nicotine decreased economic demand for sucrose, (b) varenicline rescued nicotine-induced reduction in economic demand for sucrose, and (c) history of varenicline treatment predicted responding for sucrose on a progressive ratio schedule of reinforcement where rats with a history of varenicline treatment responded significantly lower for sucrose across nicotine doses than rats that had not been exposed to varenicline. The results of Experiment 2 largely confirmed that nicotine decreases motivation for sucrose using a passive consumption protocol and that varenicline rescues this effect. Overall, these findings suggest that varenicline interacts with the effects of nicotine by restoring nicotine-induced reduction in motivation for appetitive rewards.

Assessment of individual differences in response to acute bupropion or varenicline treatment using a long-access nicotine self-administration model and behavioral economics in female rats.

Bupropion and varenicline are widely prescribed pharmacological treatments for smoking cessation. These treatments are only marginally effective in clinical populations but most preclinical studies show that they are effective in decreasing self-administration in rats on a group level. The present study investigated individual differences in responding to bupropion or varenicline in a preclinical model of long-access to nicotine (0.03 mg/kg/inf; 12 h/day) in female rats. Rats were first assessed for their individual economic demand for nicotine and for their individual performance in open field and elevated plus maze prior to nicotine access and during withdrawal. Rats were then tested for the acute effects of bupropion, varenicline, and yohimbine. We found that neither bupropion nor varenicline decreased responding for nicotine on test days. On the contrary, a moderate dose of bupropion (30 mg/kg) significantly increased responding for nicotine. We also found that rats with higher demand for nicotine were more sensitive to pretreatment with yohimbine which resulted in increased responding for nicotine during the dose-effect tests. Finally, we show that rats that had a higher demand for nicotine also were more persistent in seeking nicotine during extinction and reinstatement tests with nicotine or yohimbine as triggers. Our findings suggest that the length of access to daily nicotine may be an important factor underlying the response to pharmacological treatments like bupropion or varenicline. Future studies modeling chronic treatment approaches that include both sexes will be needed to further extend our findings.

Rats choose high doses of nicotine in order to compensate for changes in its price and availability.

Restricting when and where smoking can occur is a major focus of public health policies in Western countries. In conjunction with increased taxation, these approaches have contributed to a reduction in smoking uptake among adolescents, yet the consequences for established smokers are less clear. In order to further explore this relationship, we developed a novel animal model of restricted nicotine self-administration. Rats were trained to choose between three doses of nicotine (15, 30 and 60 µg/kg/infusion) under conditions where nicotine was (1) freely available at a low cost (20-second post-infusion time-out, fixed-ratio 1 [FR1]), (2) available under restricted access at a low cost (300-second post-infusion time-out, FR1), or (3) freely available at a high cost (20-second post-infusion time-out, FR5). We demonstrate that as access to nicotine is restricted or when cost increases, rats compensate for these changes by increasing their intake of the highest dose of nicotine available. This preference was impervious to treatment with the smoking cessation medication varenicline, but was reduced when the cost of the highest dose only was increased, or when nicotine was again made freely available at a low cost. These results provide the first evidence in rats that nicotine availability and cost influence nicotine choice independently of variations in nicotine and context exposure. They imply that established smokers may compensate for changes in the availability and cost of tobacco by increasing their rate of smoking when they are free to do so.

Smoking Cessation and Cardiac Rehabilitation: A Priority!

Cardiac rehabilitation programmes afford the opportunity to enhance cardiovascular health and reduce the risk of subsequent cardiac events. They permit the management of cardiac risk factors while addressing significant psychosocial and vocational issues. Tobacco addiction is the most important of the modifiable cardiac risk factors, and smoking cessation is the most important secondary prevention strategy. Cessation is more likely when cessation pharmacotherapy is accompanied by supportive advice and strategic assistance. A systematic approach to the delivery of cessation services, such as the Ottawa Model of Smoking Cessation, greatly enhances the likelihood of success. Cardiac rehabilitation programmes are ideal venues for the delivery of such programmes.