Mouse model of operant oral nicotine self-administration

Authors

• C Duval
• M Ji
• X Li

Abstract

Nicotine is an active ingredient that leads to addiction to tobacco products. Nicotine binds to the nicotinic acetylcholine receptors (nAChRs) of the brain and has many downstream effects, including positive reinforcement that leads to habit formation and addiction to nicotine. However, there is no established behavioral procedure to examine the reinforcing effects of nicotine in mice. We examine if oral nicotine self-administration can work as an effective model of nicotine reinforcement. We found that mice orally consume nicotine solutions. Using a free choice procedure in which mice had access to nicotine solutions and water daily for 24 hours, mice readily consumed nicotine solutions. As the concentration of the nicotine solutions increased, mice consumed more nicotine per day despite consuming less volume of the solutions. We also found sex differences: female mice consumed more nicotine than males. We were also able to train mice to operantly respond for oral administration of nicotine. Mice were placed in operant chambers where they had access to a nicotine solution upon pressing a lever and they learned to respond for oral nicotine. However, once mice learned to operantly respond for oral nicotine, behavioral responses were not sensitive to manipulations including differential concentrations of nicotine solution and pharmacological challenges with nicotinic receptor agonists and antagonists. These observations suggest that behavior reinforced by oral nicotine is highly habitual. Our operant self-administration of oral nicotine procedure has potential to be an effective model for investigating neural mechanisms of the reinforcing and habitual effects of nicotine.

Scientific Focus Area: Neuroscience

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