Nicotine inhibits the VTA-to-amygdala dopamine pathway to promote anxiety.
Neuron. 2021-07-01; :
DOI: 10.1016/j.neuron.2021.06.013
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Nguyen C(1), Mondoloni S(2), Le Borgne T(1), Centeno I(2), Come M(1), Jehl J(1), Solié C(1), Reynolds LM(1), Durand-de Cuttoli R(2), Tolu S(2), Valverde S(2), Didienne S(1), Hannesse B(2), Fiancette JF(3), Pons S(4), Maskos U(4), Deroche-Gamonet V(3), Dalkara D(5), Hardelin JP(1), Mourot A(1), Marti F(6), Faure P(7).
Author information:
(1)ESPCI, Laboratoire de plasticité du cerveau UMR8249, 10 rue Vauquelin, 75005 Paris, France; Sorbonne Université, Inserm, UMR8246 CNRS, Neuroscience Paris Seine – IBPS, 75005 Paris, France.
(2)Sorbonne Université, Inserm, UMR8246 CNRS, Neuroscience Paris Seine – IBPS, 75005 Paris, France.
(3)Neurocentre Magendie, Inserm U1215, Université de Bordeaux, 146 rue Léo Saignat, 33077 Bordeaux, France.
(4)Institut Pasteur, Unité Neurobiologie intégrative des systèmes cholinergiques, Département de neuroscience, 75724 Paris Cedex, France.
(5)Sorbonne Université, Inserm, CNRS, Institut de la Vision, Paris, France.
(6)ESPCI, Laboratoire de plasticité du cerveau UMR8249, 10 rue Vauquelin, 75005 Paris, France; Sorbonne Université, Inserm, UMR8246 CNRS, Neuroscience Paris Seine – IBPS, 75005 Paris, France. Electronic address: .
(7)ESPCI, Laboratoire de plasticité du cerveau UMR8249, 10 rue Vauquelin, 75005 Paris, France; Sorbonne Université, Inserm, UMR8246 CNRS, Neuroscience Paris Seine – IBPS, 75005 Paris, France. Electronic address: .
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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