TRPV1 deletion enhances consumption but not seeking behavior for sweetened nicotine solution in male mice

Nicotine is not only the primary addictive component of smoking but it also greatly contributes to the sensory properties of tobacco. Consequently, investigating the orosensory effects of nicotine is essential to understand the vulnerability to initial stages of cigarette smoking. Within the oral cavity, transient receptor potential vanilloid 1 receptors (TRPV1Rs) are responsible for sensations such as chili peppers-induced pungency and oral burning, and these receptors are activated by nicotine. Here, we hypothesized that TRPV1Rs contribute to the irritant and burning sensations induced by nicotine, and that its dysfunction may promote vulnerability to nicotine addiction. To test this, adult male mice with invalidation of the TRPV1R gene were exposed to oral self-administration of nicotine solution allowing us to examine the key steps of the addictive process, namely acquisition and maintenance of taking behavior, motivation to obtain the drug and nicotine seeking behavior. We found that in comparison to wild-type mice, knockout (KO) mice consumed significantly higher amounts of nicotine both at the training dose and across the dose-response curve. Despite the increased consumption of nicotine by KO mice, this did not promote greater motivational properties of nicotine or cue-induced reinstatement of drug-seeking behavior in the absence of reinforcer. Altogether, these results suggest that decreased function of the TRPV1Rs prevents the development of aversion to nicotine solution, which may contribute to a heightened vulnerability to nicotine initiation.