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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•Nicotine injection activates or inhibits distinct VTA dopaminergic subpopulations•NAc-projecting neurons are excited by nicotine, and their activation is reinforcing•Amygdala-projecting neurons are inhibited by nicotine, and their silencing is anxiogenic•Nicotine-mediated anxiety is prevented by activating VTA-amygdala DA neurons
Nicotine promotes anxiety in addition to its reinforcing properties. Nguyen et al. demonstrate that nicotine activates nucleus-accumbens-projecting dopamine neurons while concomitantly inhibiting amygdala-projecting ones. Bidirectionally manipulating these two pathways using optogenetics reveals that their opposing responses differentially drive the rewarding and anxiogenic effects of nicotine.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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Provider: - Institution: - Data provided by Europeana Collections- Présentation musicale : Partit. orch.- All metadata published by Europeana are available free of restriction under the Creative ...Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
Provider: - Institution: - Data provided by Europeana Collections- Présentation musicale : Partit. orch.- All metadata published by Europeana are available free of restriction under the Creative ...Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
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