Dopamine neurons projecting to medial shell of the nucleus accumbens drive heroin reinforcement
The dopamine (DA) hypothesis posits the increase of mesolimbic dopamine levels as a defining commonality of addictive drugs, initially causing reinforcement, eventually leading to compulsive consumption. While much experimental evidence from psychostimulants supports this hypothesis, it has been cha...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-10-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/39945 |
| _version_ | 1829096803694280704 |
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| author | Julie Corre Ruud van Zessen Michaël Loureiro Tommaso Patriarchi Lin Tian Vincent Pascoli Christian Lüscher |
| author_facet | Julie Corre Ruud van Zessen Michaël Loureiro Tommaso Patriarchi Lin Tian Vincent Pascoli Christian Lüscher |
| author_sort | Julie Corre |
| collection | DOAJ |
| description | The dopamine (DA) hypothesis posits the increase of mesolimbic dopamine levels as a defining commonality of addictive drugs, initially causing reinforcement, eventually leading to compulsive consumption. While much experimental evidence from psychostimulants supports this hypothesis, it has been challenged for opioid reinforcement. Here, we monitor genetically encoded DA and calcium indicators as well as cFos in mice to reveal that heroin activates DA neurons located in the medial part of the VTA, preferentially projecting to the medial shell of the nucleus accumbens (NAc). Chemogenetic and optogenetic manipulations of VTA DA or GABA neurons establish a causal link to heroin reinforcement. Inhibition of DA neurons blocked heroin self-administration, while heroin inhibited optogenetic self-stimulation of DA neurons. Likewise, heroin occluded the self-inhibition of VTA GABA neurons. Together, these experiments support a model of disinhibition of a subset of VTA DA neurons in opioid reinforcement. |
| first_indexed | 2024-04-11T09:03:22Z |
| format | Article |
| id | doaj.art-f4505274ee6c4dfeba44298e8512327a |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:03:22Z |
| publishDate | 2018-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-f4505274ee6c4dfeba44298e8512327a2022-12-22T04:32:43ZengeLife Sciences Publications LtdeLife2050-084X2018-10-01710.7554/eLife.39945Dopamine neurons projecting to medial shell of the nucleus accumbens drive heroin reinforcementJulie Corre0Ruud van Zessen1Michaël Loureiro2https://orcid.org/0000-0002-5915-5627Tommaso Patriarchi3Lin Tian4https://orcid.org/0000-0001-7012-6926Vincent Pascoli5Christian Lüscher6https://orcid.org/0000-0001-7917-4596Department of Basic Neurosciences, Medical Faculty, University of Geneva, Geneva, SwitzerlandDepartment of Basic Neurosciences, Medical Faculty, University of Geneva, Geneva, SwitzerlandDepartment of Basic Neurosciences, Medical Faculty, University of Geneva, Geneva, SwitzerlandSchool of Medicine, Department of Biochemistry and Molecular Medicine, University of California Davis, California, United StatesSchool of Medicine, Department of Biochemistry and Molecular Medicine, University of California Davis, California, United StatesDepartment of Basic Neurosciences, Medical Faculty, University of Geneva, Geneva, SwitzerlandDepartment of Basic Neurosciences, Medical Faculty, University of Geneva, Geneva, Switzerland; Service of Neurology, University of Geneva Hospital, Geneva, SwitzerlandThe dopamine (DA) hypothesis posits the increase of mesolimbic dopamine levels as a defining commonality of addictive drugs, initially causing reinforcement, eventually leading to compulsive consumption. While much experimental evidence from psychostimulants supports this hypothesis, it has been challenged for opioid reinforcement. Here, we monitor genetically encoded DA and calcium indicators as well as cFos in mice to reveal that heroin activates DA neurons located in the medial part of the VTA, preferentially projecting to the medial shell of the nucleus accumbens (NAc). Chemogenetic and optogenetic manipulations of VTA DA or GABA neurons establish a causal link to heroin reinforcement. Inhibition of DA neurons blocked heroin self-administration, while heroin inhibited optogenetic self-stimulation of DA neurons. Likewise, heroin occluded the self-inhibition of VTA GABA neurons. Together, these experiments support a model of disinhibition of a subset of VTA DA neurons in opioid reinforcement.https://elifesciences.org/articles/39945opioidsaddictiondopamine |
| spellingShingle | Julie Corre Ruud van Zessen Michaël Loureiro Tommaso Patriarchi Lin Tian Vincent Pascoli Christian Lüscher Dopamine neurons projecting to medial shell of the nucleus accumbens drive heroin reinforcement eLife opioids addiction dopamine |
| title | Dopamine neurons projecting to medial shell of the nucleus accumbens drive heroin reinforcement |
| title_full | Dopamine neurons projecting to medial shell of the nucleus accumbens drive heroin reinforcement |
| title_fullStr | Dopamine neurons projecting to medial shell of the nucleus accumbens drive heroin reinforcement |
| title_full_unstemmed | Dopamine neurons projecting to medial shell of the nucleus accumbens drive heroin reinforcement |
| title_short | Dopamine neurons projecting to medial shell of the nucleus accumbens drive heroin reinforcement |
| title_sort | dopamine neurons projecting to medial shell of the nucleus accumbens drive heroin reinforcement |
| topic | opioids addiction dopamine |
| url | https://elifesciences.org/articles/39945 |
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