Nicotine engages a VTA-NAc feedback loop to inhibit amygdala-projecting dopamine neurons and induce anxiety-like behaviors
Abstract Nicotine activates ventral tegmental area (VTA) dopaminergic (DA) neurons projecting to the nucleus accumbens (NAc) to drive its reinforcing effects. Simultaneously, nicotine inhibits those projecting to the amygdala (Amg) to mediate anxiety-like behavior through a process that remains unkn...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61180-8 |
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| author | Tïnaïg Le Borgne Claire Nguyen Eléonore Vicq Joachim Jehl Clément Solié Nicolas Guyon Louison Daussy Aylin Gulmez Lauren M. Reynolds Sarah Mondoloni Stéfania Tolu Stéphanie Pons Uwe Maskos Emmanuel Valjent Alexandre Mourot Philippe Faure Fabio Marti |
| author_facet | Tïnaïg Le Borgne Claire Nguyen Eléonore Vicq Joachim Jehl Clément Solié Nicolas Guyon Louison Daussy Aylin Gulmez Lauren M. Reynolds Sarah Mondoloni Stéfania Tolu Stéphanie Pons Uwe Maskos Emmanuel Valjent Alexandre Mourot Philippe Faure Fabio Marti |
| author_sort | Tïnaïg Le Borgne |
| collection | DOAJ |
| description | Abstract Nicotine activates ventral tegmental area (VTA) dopaminergic (DA) neurons projecting to the nucleus accumbens (NAc) to drive its reinforcing effects. Simultaneously, nicotine inhibits those projecting to the amygdala (Amg) to mediate anxiety-like behavior through a process that remains unknown. Here, we show that in male mice, NAc- and Amg-projecting DA neurons respond with similar polarities to ethanol and nicotine, suggesting a shared network-based mechanism underlying the inhibitory effect of these otherwise pharmacologically-distinct drugs. Selective activation of NAc-projecting DA neurons, using genetic or optogenetic strategies, produced inhibition of Amg-projecting DA neurons, through a GABAergic feedback loop. Furthermore, optogenetically silencing this feedback loop prevented nicotine from inducing both inhibition of DA neurons and anxiety-like behavior. Therefore, nicotine-induced inhibition of the VTA-Amg DA pathway results from a VTA-NAc inhibitory feedback loop, mediating anxiety-like behavior. |
| format | Article |
| id | doaj-art-eb55e5906ec94850a111a62331b8716e |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-eb55e5906ec94850a111a62331b8716e2025-08-20T03:45:31ZengNature PortfolioNature Communications2041-17232025-07-0116111510.1038/s41467-025-61180-8Nicotine engages a VTA-NAc feedback loop to inhibit amygdala-projecting dopamine neurons and induce anxiety-like behaviorsTïnaïg Le Borgne0Claire Nguyen1Eléonore Vicq2Joachim Jehl3Clément Solié4Nicolas Guyon5Louison Daussy6Aylin Gulmez7Lauren M. Reynolds8Sarah Mondoloni9Stéfania Tolu10Stéphanie Pons11Uwe Maskos12Emmanuel Valjent13Alexandre Mourot14Philippe Faure15Fabio Marti16Plasticité du Cerveau CNRS UMR8249, École supérieure de physique et de chimie industrielles de la Ville de Paris (ESPCI Paris)Neuroscience Paris Seine CNRS UMR 8246 INSERM U1130, Institut de Biologie Paris Seine, Sorbonne UniversitéPlasticité du Cerveau CNRS UMR8249, École supérieure de physique et de chimie industrielles de la Ville de Paris (ESPCI Paris)Plasticité du Cerveau CNRS UMR8249, École supérieure de physique et de chimie industrielles de la Ville de Paris (ESPCI Paris)Plasticité du Cerveau CNRS UMR8249, École supérieure de physique et de chimie industrielles de la Ville de Paris (ESPCI Paris)Plasticité du Cerveau CNRS UMR8249, École supérieure de physique et de chimie industrielles de la Ville de Paris (ESPCI Paris)Plasticité du Cerveau CNRS UMR8249, École supérieure de physique et de chimie industrielles de la Ville de Paris (ESPCI Paris)Plasticité du Cerveau CNRS UMR8249, École supérieure de physique et de chimie industrielles de la Ville de Paris (ESPCI Paris)Plasticité du Cerveau CNRS UMR8249, École supérieure de physique et de chimie industrielles de la Ville de Paris (ESPCI Paris)Neuroscience Paris Seine CNRS UMR 8246 INSERM U1130, Institut de Biologie Paris Seine, Sorbonne UniversitéNeuroscience Paris Seine CNRS UMR 8246 INSERM U1130, Institut de Biologie Paris Seine, Sorbonne UniversitéUnité Neurobiologie intégrative des systèmes cholinergiques, Département de neuroscience, Institut PasteurUnité Neurobiologie intégrative des systèmes cholinergiques, Département de neuroscience, Institut PasteurInstitut des Neurosciences de Montpellier, Université de Montpellier, INSERM U1298Plasticité du Cerveau CNRS UMR8249, École supérieure de physique et de chimie industrielles de la Ville de Paris (ESPCI Paris)Plasticité du Cerveau CNRS UMR8249, École supérieure de physique et de chimie industrielles de la Ville de Paris (ESPCI Paris)Plasticité du Cerveau CNRS UMR8249, École supérieure de physique et de chimie industrielles de la Ville de Paris (ESPCI Paris)Abstract Nicotine activates ventral tegmental area (VTA) dopaminergic (DA) neurons projecting to the nucleus accumbens (NAc) to drive its reinforcing effects. Simultaneously, nicotine inhibits those projecting to the amygdala (Amg) to mediate anxiety-like behavior through a process that remains unknown. Here, we show that in male mice, NAc- and Amg-projecting DA neurons respond with similar polarities to ethanol and nicotine, suggesting a shared network-based mechanism underlying the inhibitory effect of these otherwise pharmacologically-distinct drugs. Selective activation of NAc-projecting DA neurons, using genetic or optogenetic strategies, produced inhibition of Amg-projecting DA neurons, through a GABAergic feedback loop. Furthermore, optogenetically silencing this feedback loop prevented nicotine from inducing both inhibition of DA neurons and anxiety-like behavior. Therefore, nicotine-induced inhibition of the VTA-Amg DA pathway results from a VTA-NAc inhibitory feedback loop, mediating anxiety-like behavior.https://doi.org/10.1038/s41467-025-61180-8 |
| spellingShingle | Tïnaïg Le Borgne Claire Nguyen Eléonore Vicq Joachim Jehl Clément Solié Nicolas Guyon Louison Daussy Aylin Gulmez Lauren M. Reynolds Sarah Mondoloni Stéfania Tolu Stéphanie Pons Uwe Maskos Emmanuel Valjent Alexandre Mourot Philippe Faure Fabio Marti Nicotine engages a VTA-NAc feedback loop to inhibit amygdala-projecting dopamine neurons and induce anxiety-like behaviors Nature Communications |
| title | Nicotine engages a VTA-NAc feedback loop to inhibit amygdala-projecting dopamine neurons and induce anxiety-like behaviors |
| title_full | Nicotine engages a VTA-NAc feedback loop to inhibit amygdala-projecting dopamine neurons and induce anxiety-like behaviors |
| title_fullStr | Nicotine engages a VTA-NAc feedback loop to inhibit amygdala-projecting dopamine neurons and induce anxiety-like behaviors |
| title_full_unstemmed | Nicotine engages a VTA-NAc feedback loop to inhibit amygdala-projecting dopamine neurons and induce anxiety-like behaviors |
| title_short | Nicotine engages a VTA-NAc feedback loop to inhibit amygdala-projecting dopamine neurons and induce anxiety-like behaviors |
| title_sort | nicotine engages a vta nac feedback loop to inhibit amygdala projecting dopamine neurons and induce anxiety like behaviors |
| url | https://doi.org/10.1038/s41467-025-61180-8 |
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