Nicotine inhibits the VTA-to-amygdala dopamine pathway to promote anxiety - Archive ouverte HAL Access content directly
Journal Articles Neuron Year : 2021

Nicotine inhibits the VTA-to-amygdala dopamine pathway to promote anxiety

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Sarah Mondoloni
Romain Durand-de Cuttoli
Deniz Dalkara

Abstract

Nicotine stimulates dopamine (DA) neurons of the ventral tegmental area (VTA) to establish and maintain reinforcement. Nicotine also induces anxiety through an as yet unknown circuitry. We found that nicotine injection drives opposite functional responses of two distinct populations of VTA DA neurons with anatomically segregated projections: it activates neurons that project to the nucleus accumbens (NAc), whereas it inhibits neurons that project to the amygdala nuclei (Amg). We further show that nicotine mediates anxiety-like behavior by acting on β2-subunit-containing nicotinic acetylcholine receptors of the VTA. Finally, using optogenetics, we bidirectionally manipulate the VTA-NAc and VTA-Amg pathways to dissociate their contributions to anxiety-like behavior. We show that inhibition of VTA-Amg DA neurons mediates anxiety-like behavior, while their activation prevents the anxiogenic effects of nicotine. These distinct subpopulations of VTA DA neurons with opposite responses to nicotine may differentially drive the anxiogenic and the reinforcing effects of nicotine.
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Dates and versions

pasteur-03300623 , version 1 (24-11-2021)

Licence

Attribution - NonCommercial - NoDerivatives - CC BY 4.0

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Claire Nguyen, Sarah Mondoloni, Tinaïg Le Borgne, Ines Centeno, Maxime Come, et al.. Nicotine inhibits the VTA-to-amygdala dopamine pathway to promote anxiety. Neuron, 2021, 109 (16), pp.2604-2615.e9. ⟨10.1016/j.neuron.2021.06.013⟩. ⟨pasteur-03300623⟩
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