Dynamic dichotomy of accumbal population activity underlies cocaine sensitization

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Abstract

Locomotor sensitization (LS) is an early behavioral adaptation to addictive drugs, driven by the increase of dopamine in the Nucleus Accumbens (NAc). However, the effect on accumbal population activity remains elusive. Here we used single cell calcium imaging in mice to record the activity of dopamine-1-receptor (D1R) and dopamine-2-receptor (D2R) expressing spiny projection neurons (SPNs) during cocaine LS. Acute exposure to cocaine elevated D1R SPN activity and reduced D2R SPN activity, albeit with high variability between neurons. During LS, the number of D1R and D2R neurons responding in opposite directions increased. Moreover, preventing LS by inhibition of the ERK signaling pathway decreased the number of cocaine responsive D1R SPNs, but had little effect on D2R SPNs. These results indicate that accumbal population dichotomy is dynamic and contains a subgroup of D1R SPNs that eventually drives LS. Insights into the drug-related activity dynamics provides a foundation for understanding the circuit-level addiction pathogenesis.

Data availability

Data and code have been made available via Zenodo: DOI: 10.5281/zenodo.5507009

The following data sets were generated

1. van Zessen R
2. Li Y
3. Marion-Poll L
4. Hulo N
5. Flakowski J
6. Lüscher C
(2021) Dynamic dichotomy of accumbal population activity underlies cocaine sensitization
Zenodo, DOI: 10.5281/zenodo.5507009.

https://doi.org/10.5281/zenodo.5507009

Article and author information

Author details

Ruud van Zessen

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:" 0000-0001-5634-6922
Yue Li

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

Competing interests
The authors declare that no competing interests exist.
Lucile Marion-Poll

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

Competing interests
The authors declare that no competing interests exist.
Nicolas Hulo

Service for Biomathematical and Biostatistical Analyses, University of Geneva, Geneva, Switzerland

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-2640-636X
Jérôme Flakowski

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:" 0000-0002-6457-3022
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

Swiss National Science Foundation (310030_189188)

Christian Lüscher

European Commission (F_Addict)

Christian Lüscher

Swiss National Science Foundation (CRSII5_186266)

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: All experiments were reviewed and approved by the Institutional Animal Care and Use Committee of the University of Geneva (GE64-20 and GE71-20)

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.