The effects of noncontingent and self-administered cytisine on body weight and meal patterns in male Sprague-Dawley rats

摘要

Rationale: Increased appetite andweight gain after cessation are deterrents for quitting smoking. Pharmacotherapies that can reduce this weight gain in ex-smokers would be invaluable, and yet are not well studied in this context. Objective: To examine the effects of extended daily exposure to intravenous cytisine, an alpha4beta2 nAChR partial agonist used for smoking cessation in some European countries, on bodyweight and patterns of food intake in rats. Methods: In the first experiment, programmed infusions of cytisine were administered over 15 h per day. Food intake, meal patterns, and weight change were examined relative to a vehicle-infused group during treatment, and in a post-cytisine phase. The second experiment examined the effects of cytisine on food intake, meal patterns, and weight change when substituted for nicotine in a self-administration protocol. Rats selfadministered nicotine and cytisine during alternating four day periods, and changes in body weight, drug infusions, and meal patterns were compared between drugs and during an extinction phase. Results: In the first experiment, cytisine-treated rats ate less and gained less weight than those that received the vehicle. This occurred primarily by a reduced frequency of meals. In the 12 day post-cytisine phase, animals maintained a lower bodyweight relative to controls throughout. In the second experiment, total pellet intake increased during cytisine substitution relative to nicotine and animals self-administered cytisine significantly less than nicotine. However, cytisine substitution maintained decreases in food intake and weight gain compared to baseline via decreases in total pellet intake and meal size. Conclusion: Cytisine administration results in decreased weight gain and changes in meal patterns dependent upon mode and pattern of administration and a previous history of nicotine administration.