Nicotine-taking and nicotine-seeking in C57Bl/6J mice without prior operant training or food restriction

• Published in: Behavioural brain research 2012-04, Vol.230 (1), p.34-39
• Main Authors: Yan, Yijin, Pushparaj, Abhiram, Gamaleddin, Islam, Steiner, Rebecca C., Picciotto, Marina R., Roder, John, Le Foll, Bernard
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Conditioning, Operant - physiology; Cues; Dependence; Dose-Response Relationship, Drug; Electroshock - adverse effects; Exploratory Behavior - drug effects; Extinction, Psychological - drug effects; Food Deprivation - physiology; Male; Mice; Mice, Inbred C57BL; Nicotine; Nicotine - administration & dosage; Nicotinic Agonists - administration & dosage; Reinforcement (Psychology); Reinforcement Schedule; Relapse; Seeking behavior; Self Administration
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2012.01.042

► We examined a model of nicotine self administration and relapse in C57Bl/6J mice. ► Reinstatement of drug-seeking behaviour was attempted by nicotine-associated cues, nicotine priming injections and footshock. ► The methodological factors of the current study are compared to those of previous publications. The ability to examine genetically engineered mice in a chronic intravenous (IV) nicotine self-administration paradigm will be a powerful tool for investigating the contribution of specific genes to nicotine reinforcement and more importantly, to relapse behavior. Here we describe a reliable model of nicotine-taking and -seeking behavior in male C57BL/6J mice without prior operant training or food restriction. Mice were allowed to self-administer either nicotine (0.03mg/kg/infusion) or saline in 2-h daily sessions under fixed ratio 1 (FR1) followed by FR2 schedules of reinforcement. In the nicotine group, a dose–response curve was measured after the nose-poke behavior stabilized. Subsequently, nose-poke behavior was extinguished and ability of cue presentations, priming injections of nicotine, or intermittent footshock to reinstate responding was assessed in both groups. C57BL/6J mice given access to nicotine exhibited high levels of nose-poke behavior and self-administered a high number of infusions as compared to mice given access to saline. After this acquisition phase, changing the unit-dose of nicotine resulted in a flat dose–response curve for nicotine-taking and subsequently reinstatement of nicotine-seeking behavior was achieved by both nicotine-associated light cue presentation and intermittent footshock. Nicotine priming injections only triggered significant reinstatement on the second consecutive day of priming. In contrast, mice previously trained to self-administer saline did not increase their responding under those conditions. These results demonstrate the ability to produce nicotine-taking and nicotine-seeking behavior in naive C57BL/6J mice without both prior operant training and food restriction. Future work will utilize these models to evaluate nicotine-taking and relapsing behavior in genetically-altered mice.