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Publication : Dynamic dichotomy of accumbal population activity underlies cocaine sensitization.

First Author  van Zessen R Year  2021
Journal  Elife Volume  10
PubMed ID  34608866 Mgi Jnum  J:349389
Mgi Id  MGI:6788598 Doi  10.7554/eLife.66048
Citation  van Zessen R, et al. (2021) Dynamic dichotomy of accumbal population activity underlies cocaine sensitization. Elife 10:e66048
abstractText  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.
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