NGUYEN, Claire; MONDOLONI, Sarah; LE BORGNE, Tinaig; CENTENO, Ines; COME, Maxime; JEHL, Joachim; SOLIE, Clement; REYNOLDS, Lauren M.; DURAND-DE CUTTOLI, Romain; TOLU, Stefania; VALVERDE, Sebastien; DIDIENNE, Steve; HANNESSE, Bernadette; FIANCETTE, Jean-Francois; PONS, Stephanie; MASKOS, Uwe; DEROCHE-GAMONET, Veronique; DALKARA, Deniz; HARDELIN, Jean Pierre; MOUROT, Alexandre; MARTI, Fabio; FAURE, Philippe

doi:10.1016/j.neuron.2021.06.013

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Neuron. 2021-08-18, vol. 109, n° 16, p. 2604-2615.e9

Resumen en inglés

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 ?2-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.< Leer menos

Palabras clave en inglés

Addiction

Amygdala

Dopamine circuits

Juxtacellular recordings

Nicotine

Nicotinic acetylcholine receptors

Nucleus accumbens

Optogenetics

Ventral tegmental area

URI

https://oskar-bordeaux.fr/handle/20.500.12278/124294

DOI

http://dx.doi.org/10.1016/j.neuron.2021.06.013

Centros de investigación

Neurocentre Magendie - U1215

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

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Palabras clave en inglés

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