Venue : salle Module 1.2
Thesis defended in french
Thesis supervisor: Stéphanie Caillé-Garnier
Tobacco products are highly addictive and their abuse is a major public health problem. In humans, this addiction constitutes an oral consummatory experience involving sensory gustatory and olfactory components. Nowadays, the role of these components is further amplified with the increasing use of new “heat not burn” tobacco products, electronic nicotine delivery device (e-cigarettes especially), where nicotine is associated with additives including flavours and sugars. Thus, the impact of additives on the behaviour of nicotine consumption must be assessed.
In this research work, we are interested in oral nicotine and the bidirectional interaction with the associated flavours. In particular, we question the secondary reinforcing properties, the effects of aromas on the palatability of nicotine and its affective coding.
It has been shown that non-pharmacological sensory stimuli become more salient when associated with nicotine. Here, we study the putative secondary reinforcement of oral stimuli by nicotine. We highlight the need for oral nicotine to be combined with additives that mask its bitter taste, to allow its volitional consumption and to be able to model the different stages of the addictive process. This process is sensitive to stimuli for consumption and reinstatement, but is unaffected by pharmacological challenges despite nicotine absorption measured by the dosage of plasma cotinine. High concentrations of nicotine solutions reveal its aversive properties and reduce oral self-administration in mice. Although we do not show the reinforcement of the incentive properties of vanilla by nicotine, we surprisingly show that the aroma itself can reinforce self-administration behaviour.
In a second chapter, we investigated the irritating properties of nicotine in a model of oral self-administration in mice genetically modified (knockout) for the thermoreceptor TRPV1 (Transient receptor potential vanilloid 1) because it is involved in harshness and it is sensitized by nicotine. We highlight that the absence of this receptor promotes nicotine consumption by reducing its oral aversion. It does not, however, have a specific role in motivation and relapse mechanisms.
Finally, because of the importance of the oral sensory effects in nicotine consummatory behavior, we studied its palatability properties. Taste reactivity tests show the aversive taste of nicotine alone and the enhancement of its palatability by the addition of aromatic additive. However this change in palatability did not result in changes in the neuronal coding, measured by the labelling of c-Fos protein in brain structures contributing to the expression of the positive and negative valence, notably the nucleus accumbens, the gustatory insular cortex, the basolateral amygdala, the habenula and the paraventricular nucleus of the thalamus. On the other hand, nicotine, flavoured or not, increased neuronal activity in all these structures.
Altogether, these results highlight the importance of nicotine association with flavour additives that can modulate its sensory perception and subsequently promote its consumption. The attractiveness of new tobacco products and their abuse potential is a public health problem that needs urgent study and regulation.
Keywords: nicotine, oral self-administration, palatability, addiction, flavours, e-cig, sensory stimuli
Dr. FERREIRA, Guillaume Président du Jury
Dr. MOULY, Anne-Marie Rapporteur
Dr. SOLINAS, Marcello Rapporteur
Dr. BEYELER, Anna Examinateur
Pr. NAASSILA, Mickaël Examinateur