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Co-activation of VTA DA and GABA neurons mediates nicotine reinforcement.

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Title: Co-activation of VTA DA and GABA neurons mediates nicotine reinforcement.
Authors: Tolu, S, Eddine, R, Marti, F, David, V, Graupner, M, Pons, S, Baudonnat, M, Husson, M, Besson, M, Reperant, C, Zemdegs, J, Pagès, C, Hay, Y A H, Lambolez, B, Caboche, J, Gutkin, B, Gardier, A M, Changeux, J-P, Faure, P, Maskos, U
Source: Molecular Psychiatry. Mar2013, Vol. 18 Issue 3, p382-393. 12p. 3 Diagrams, 2 Graphs.
Subjects: GABA, Nicotinic acetylcholine receptors, Interneurons, Nicotine addiction, Dopamine
Abstract: Smoking is the most important preventable cause of mortality and morbidity worldwide. This nicotine addiction is mediated through the nicotinic acetylcholine receptor (nAChR), expressed on most neurons, and also many other organs in the body. Even within the ventral tegmental area (VTA), the key brain area responsible for the reinforcing properties of all drugs of abuse, nicotine acts on several different cell types and afferents. Identifying the precise action of nicotine on this microcircuit, in vivo, is important to understand reinforcement, and finally to develop efficient smoking cessation treatments. We used a novel lentiviral system to re-express exclusively high-affinity nAChRs on either dopaminergic (DAergic) or γ-aminobutyric acid-releasing (GABAergic) neurons, or both, in the VTA. Using in vivo electrophysiology, we show that, contrary to widely accepted models, the activation of GABA neurons in the VTA plays a crucial role in the control of nicotine-elicited DAergic activity. Our results demonstrate that both positive and negative motivational values are transmitted through the dopamine (DA) neuron, but that the concerted activity of DA and GABA systems is necessary for the reinforcing actions of nicotine through burst firing of DA neurons. This work identifies the GABAergic interneuron as a potential target for smoking cessation drug development. [ABSTRACT FROM AUTHOR]
Copyright of Molecular Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Co-activation of VTA DA and GABA neurons mediates nicotine reinforcement.
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  Data: <searchLink fieldCode="AR" term="%22Tolu%2C+S%22">Tolu, S</searchLink><br /><searchLink fieldCode="AR" term="%22Eddine%2C+R%22">Eddine, R</searchLink><br /><searchLink fieldCode="AR" term="%22Marti%2C+F%22">Marti, F</searchLink><br /><searchLink fieldCode="AR" term="%22David%2C+V%22">David, V</searchLink><br /><searchLink fieldCode="AR" term="%22Graupner%2C+M%22">Graupner, M</searchLink><br /><searchLink fieldCode="AR" term="%22Pons%2C+S%22">Pons, S</searchLink><br /><searchLink fieldCode="AR" term="%22Baudonnat%2C+M%22">Baudonnat, M</searchLink><br /><searchLink fieldCode="AR" term="%22Husson%2C+M%22">Husson, M</searchLink><br /><searchLink fieldCode="AR" term="%22Besson%2C+M%22">Besson, M</searchLink><br /><searchLink fieldCode="AR" term="%22Reperant%2C+C%22">Reperant, C</searchLink><br /><searchLink fieldCode="AR" term="%22Zemdegs%2C+J%22">Zemdegs, J</searchLink><br /><searchLink fieldCode="AR" term="%22Pagès%2C+C%22">Pagès, C</searchLink><br /><searchLink fieldCode="AR" term="%22Hay%2C+Y+A+H%22">Hay, Y A H</searchLink><br /><searchLink fieldCode="AR" term="%22Lambolez%2C+B%22">Lambolez, B</searchLink><br /><searchLink fieldCode="AR" term="%22Caboche%2C+J%22">Caboche, J</searchLink><br /><searchLink fieldCode="AR" term="%22Gutkin%2C+B%22">Gutkin, B</searchLink><br /><searchLink fieldCode="AR" term="%22Gardier%2C+A+M%22">Gardier, A M</searchLink><br /><searchLink fieldCode="AR" term="%22Changeux%2C+J-P%22">Changeux, J-P</searchLink><br /><searchLink fieldCode="AR" term="%22Faure%2C+P%22">Faure, P</searchLink><br /><searchLink fieldCode="AR" term="%22Maskos%2C+U%22">Maskos, U</searchLink>
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  Data: Smoking is the most important preventable cause of mortality and morbidity worldwide. This nicotine addiction is mediated through the nicotinic acetylcholine receptor (nAChR), expressed on most neurons, and also many other organs in the body. Even within the ventral tegmental area (VTA), the key brain area responsible for the reinforcing properties of all drugs of abuse, nicotine acts on several different cell types and afferents. Identifying the precise action of nicotine on this microcircuit, in vivo, is important to understand reinforcement, and finally to develop efficient smoking cessation treatments. We used a novel lentiviral system to re-express exclusively high-affinity nAChRs on either dopaminergic (DAergic) or γ-aminobutyric acid-releasing (GABAergic) neurons, or both, in the VTA. Using in vivo electrophysiology, we show that, contrary to widely accepted models, the activation of GABA neurons in the VTA plays a crucial role in the control of nicotine-elicited DAergic activity. Our results demonstrate that both positive and negative motivational values are transmitted through the dopamine (DA) neuron, but that the concerted activity of DA and GABA systems is necessary for the reinforcing actions of nicotine through burst firing of DA neurons. This work identifies the GABAergic interneuron as a potential target for smoking cessation drug development. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Molecular Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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