Nicotine-taking and nicotine-seeking in C57Bl/6J mice without prior operant training or food restriction.
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.
Translational Addiction Research Laboratory, Neuroscience Department, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Yijin
Y
Yan
Abhiram
A
Pushparaj
Islam
I
Gamaleddin
Rebecca C
RC
Steiner
Marina R
MR
Picciotto
John
J
Roder
Bernard
B
Le Foll
D000704:Analysis of Variance; D000818:Animals; D003216:Conditioning, Operant / Q000502:physiology*; D003463:Cues; D004305:Dose-Response Relationship, Drug; D004597:Electroshock / Q000009:adverse effects; D005106:Exploratory Behavior / Q000187:drug effects; D005108:Extinction, Psychological / Q000187:drug effects; D005508:Food Deprivation / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration
D018722:Nicotinic Agonists; D009538:Nicotine