Dopamine neurons projecting to medial shell of the nucleus accumbens drive heroin reinforcement
- University of Geneva, Switzerland
- University of California Davis, United States
- University of Geneva Hospital, Switzerland
Figures
Figure 1
Heroin self-administration.
(a), Schematic of behavioral setup for self-administration experiments in (d-g). (b), Day-to-day schedule of experiment for (d–g). (c), Detail of the sequence of events following a press on the …
Figure 2
Heroin increases DA levels in the NAc via enhanced VTA DA neuron activity.
(a) Fluorescence in response to five neuromodulators in HEK293 cells expressing dLight1 (DYN: dynorphin; GLU: glutamate; 5HT: serotonin; NE: norepinephrine). Data are presented as median with 25/75 …
Figure 3
Heroin activates NAc projecting DA neurons in the medial VTA.
(a), Schematic of experiment for (b-e); (b), TH (left, red), cFos (middle, green) staining of VTA DA neurons and co-localization of TH- and cFos-expressing neurons (right) after one day of either …
Figure 4
Chemogenetic inhibition of VTA DA neurons suppresses heroin self-administration.
(a), Schematic of the experiment for (b-e); (b), Left, VTA of DTA-Cre+ mice were bilaterally injected with the inhibitory DREADD hM4D. Right, coronal confocal images of infected VTA. (c), Raster …
Figure 5
Heroin occludes optogenetic self-stimulation of VTA DA neurons.
(a), Schematic of the experiment for (b-f); (b), Left, VTA of DAT-Cre+ mice was bilaterally injected with a floxed version of the excitatory opsin ChR2. Right, coronal confocal images of infected …
Figure 6
Heroin occludes reinforcing effects of self-inhibition of VTA GABA neurons.
(a), Schematic of the experiment for b-f; (b), Left, VTA of GAD-Cre+ mice was bilaterally injected with a floxed version of the inhibitory opsin Arch3.0. Right, coronal confocal images of infected …
Tables
Key resources table
| Reagent type (species) or resource | Designation | Source or reference | Identifiers | Additional information |
|---|---|---|---|---|
| Genetic reagent (M. musculus) | DATIREScre | The Jackson Laboratory (www.jax.org) | MGI:3689434 | |
| Genetic reagent (M. musculus) | Gad2tm2(cre)Zjh | The Jackson Laboratory (http://www.jax.org) | MGI:4418713 | |
| Cell line (homo sapiens, human) | HEK293T | ATCC | Cat# CRL-1573 | |
| Recombinant DNA reagent | AAV9-CAG-dLight1.1 | Dr. Lin Tian, University of California Davis | Patriarchi et al., 2018 | |
| Recombinant DNA reagent | AAVDJ-EF1a-DIO-GCaMP6m | Stanford Vector Core | Cat# GVVC-AAV-94 | |
| Recombinant DNA reagent | AAV8-hSyn-DIO-ChrimsonR-tdTo | UNC Vector Core | ||
| Recombinant DNA reagent | AAV5-hSyn-DIO-HM4D(Gi)-mCherry | UNC Vector Core | ||
| Recombinant DNA reagent | AAV5-EF1a-DIO-ChR2(H134R)-eYFP | UNC Vector Core | ||
| Recombinant DNA reagent | AAV5-EF1a-DIO-eArch3.0-eYFP | UNC Vector Core | ||
| Peptide, recombinant protein | CTB (Alexa FluorTM 555 Conjugate) | Invitrogen/Thermo Fisher | Cat# C34776 | |
| Peptide, recombinant protein | CTB (Alexa FluorTM 488 Conjugate) | Invitrogen/Thermo Fisher | Cat# C34775 | |
| Peptide, recombinant protein | CTB (Alexa FluorTM 647 Conjugate) | Invitrogen/Thermo Fisher | Cat# C34778 | |
| Chemical compound, drug | Diacetylmorphine (heroin) | DiaMo Narcotics GmbH | DIAPHIN | |
| Chemical compound, drug | Citalopram | Cayman Chemical | Cat# 14572 | |
| Chemical compound, drug | Reboxetine | Tocris | Cat# 1982 | |
| Chemical compound, drug | Cocaine | University Hospital of Geneva | ||
| Antibody | Anti-cFos | Santa Cruz Biotechnology | RRID: AB_2106783 | (dilution 1:5000) |
| Antibody | Anti-Tyrosine Hydroxylase | Sigma-Altrich | Cat# T2928 | (dilution 1:500) |
| Antibody | Anti- GFP | Invitrogen/Thermo Fisher | Cat# 11122 | (dilution 1:500) |
| Software, algorithm | Prism 7.02 | Graphpad | ||
| Software, algorithm | MATLAB R2017a | Mathworks | ||
| Software, algorithm | Synapse | Tucker-Davis Technologies |
Additional files
-
Supplementary file 1
Statistics table
- https://doi.org/10.7554/eLife.39945.008
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Transparent reporting form
- https://doi.org/10.7554/eLife.39945.009
