The Effects of a Neutral Cannabinoid-1 Receptor Antagonist on Intravenous Nicotine Self Administration Behaviour

Introduction: Tobacco dependence is a chronic disorder that carries the risk of relapse at any time point during abstinence. It is a major health issue in the world and current pharmacotherapies have had limited efficacy. Therefore, development and validation of novel treatments are required. Objective: Investigate the novel neutral cannabinoid-1 receptor antagonist AM4113 on nicotine (main psychoactive ingredient in tobacco)-taking behaviour in animals. Methods: Using the nicotine intravenous- and food control- self administration paradigms, we tested the acute and chronic (10-days) effects of AM4113 on nicotine- and food-taking behaviour. Results: Acute AM4113 treatments (1-, 3-, 10-mg/kg) reduced nicotine self administration. Chronic AM4113 administration (10mg/kg) produced a sustained reduction of nicotine-taking behaviour during the course of the treatment. In the similar food control self administration experiments, AM4113 overall produced no effect. Conclusion: AM4113 can attenuate nicotine-taking behaviour and its effect is sustained under chronic treatment.MAS

Translational strategies for therapeutic development in nicotine addiction: Rethinking the conventional bench to bedside approach

International audienceTobacco produces an impressive burden of disease resulting in premature death in half of users. Despite effective smoking cessation medications (nicotine replacement therapies, bupropion and varenicline), there is a very high rate of relapse following quit attempts. The use of efficient strategies for the development of novel treatments is a necessity. A 'bench to bedside strategy' was initially used to develop cannabinoid CB1 receptor antagonists for the treatment of nicotine addiction. Unfortunately, after being tested on experimental animals, what seemed to be an interesting approach for the treatment of nicotine addiction resulted in serious unwanted side effects when tested in humans. Current research is focusing again on pre-clinical models in an effort to eliminate unwanted side effects while preserving the initially observed efficacy. A 'bed side to bench strategy' was used to study the role of the insula (part of the frontal cortex) in nicotine addiction. This line of research started based on clinical observations that patients suffering stroke-induced lesions to the insula showed a greater likelihood to report immediate smoking cessation without craving or relapse. Subsequently, animal models of addiction are used to explore the role of insula in addiction. Due to the inherent limitations existing in clinical versus preclinical studies, the possibility of close interaction between both models seems to be critical for the successful development of novel therapeutic strategies for nicotine dependence