Impact of acute and chronic nicotine administration on midbrain dopaminergic neuron activity and related behaviours in TRPV1 knock‐out juvenile mice

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Allain, Anne‐Emilie | Aribo, Oceane | Medrano, Maria‐Carmen | Fournier, Marie‐line | Bertrand, Sandrine, S | Caille, Stephanie

Edité par CCSD ; Wiley -

International audience. The addictive properties of nicotine, the main alkaloid in tobacco and tobaccoderived products, largely depend on its action on the activity of midbrain dopamine (DA) neurons. The transient receptor potential vanilloid 1 (TRPV1) channel has also been examined as an emerging contributor to addictionrelated symptoms due to its ability to modulate midbrain neurons. Thus, the objective of our study was to explore the role of TRPV1 receptors (TRPV1Rs) on nicotine-induced behaviours and associated response of DA neuron activity. Both wild type juvenile mice and juvenile mice with invalidation of the TRPV1R gene were exposed to acute or chronic nicotine 0.3 mg/kg administration. We analysed locomotor activity in response to the drug. In addition, we performed cell-attached and whole-cell recordings from ventral tegmental area (VTA) neurons after nicotine exposure. Our results showed that the genetic deletion of TRPV1Rs reduced nicotine-induced locomotor sensitization. In addition, it provided evidence in support of TRPV1Rs being regulators of inhibitory synaptic transmission in the VTA. However, TRPV1Rs did not seem to modulate either nicotine-induced conditioning place preference or nicotineevoked electrical activity of DA neurons. In conclusion, TRPV1Rs modulate nicotine-induced psychomotor sensitization in mice independently of a control on VTA DA neuron activity. Thus, TRPV1R control may depend on another key player of the mesolimbic circuit.

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