Dopamine neurons projecting to medial shell of the nucleus accumbens drive heroin reinforcement
- University of Geneva, Switzerland
- University of California, Davis, United States
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)
Article and author information
Author details
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.
Reviewing Editor
- Lisa M Monteggia, UT Southwestern Medical Center, United States
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.
Version history
- Received: July 11, 2018
- Accepted: October 17, 2018
- Accepted Manuscript published: October 30, 2018 (version 1)
- Version of Record published: October 30, 2018 (version 2)
Copyright
© 2018, Corre et al.
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.
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Dopamine neurons projecting to medial shell of the nucleus accumbens drive heroin reinforcement
eLife 7:e39945.
https://doi.org/10.7554/eLife.39945
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