Dopamine neurons projecting to medial shell of the nucleus accumbens drive heroin reinforcement

Abstract
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Abstract

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.

Data availability

The raw data are available via Zenodo (https://zenodo.org/record/1471574#.W9K7YfaYSUk)

The following data sets were generated

1. Corre J
2. Van Zessen R
3. Loureiro M
4. Patriarchi T
5. Tian L
6. Pascoli V
7. Lüscher C
(2018) Dataset from Dopamine neurons projecting to medial shell of the nucleus accumbens drive heroin reinforcement
Available at Zenodo.

https://zenodo.org/record/1471574#.W9L6EhNKg3h

Article and author information

Author details

Julie Corre

Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland

Competing interests
The authors declare that no competing interests exist.
Ruud van Zessen

Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland

Competing interests
The authors declare that no competing interests exist.
Michaël Loureïro

Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-5915-5627
Tommaso Patriarchi

Department of Biochemistry and Molecular Medicine, University of California, Davis, Davis, United States

Competing interests
The authors declare that no competing interests exist.
Lin Tian

Department of Biochemistry and Molecular Medicine, University of California, Davis, Davis, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-7012-6926
Vincent Pascoli

Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland

Competing interests
The authors declare that no competing interests exist.
Christian Lüscher

Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland

For correspondence
Christian.Luscher@unige.ch

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-7917-4596

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030B_170266)

Christian Lüscher

European Commission (MeSSI)

Christian Lüscher

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with Swiss law (LPA). All of the animals were handled according to approved institutional animal care and use committee of Unige. The protocol was approved by the Committee on the Ethics of Animal Experiments of canton of Geneva (Permit Number: GE-128-16). Every effort was made to minimize suffering.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.