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

Tannous S(1), Darlot F(1), Salafranque Y(1), Cador M(1), Caille S(2).

Author information:
(1)Univ. Bordeaux, CNRS, EPHE, INCIA, UMR5287, F-33000 Bordeaux, France.
(2)Univ. Bordeaux, CNRS, EPHE, INCIA, UMR5287, F-33000 Bordeaux, France.
Electronic address: .

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.

Copyright © 2025 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.pbb.2025.174054
PMID: 40581052 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus