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Stochastic synaptic plasticity underlying compulsion in a model of addiction

Published in Nature. 2018, vol. 564, no. 7736, p. 366-371
Abstract Activation of the mesolimbic dopamine system reinforces goal-directed behaviours. With repetitive stimulation-for example, by chronic drug abuse-the reinforcement may become compulsive and intake continues even in the face of major negative consequences. Here we gave mice the opportunity to optogenetically self-stimulate dopaminergic neurons and observed that only a fraction of mice persevered if they had to endure an electric shock. Compulsive lever pressing was associated with an activity peak in the projection terminals from the orbitofrontal cortex (OFC) to the dorsal striatum. Although brief inhibition of OFC neurons temporarily relieved compulsive reinforcement, we found that transmission from the OFC to the striatum was permanently potentiated in persevering mice. To establish causality, we potentiated these synapses in vivo in mice that stopped optogenetic self-stimulation of dopamine neurons because of punishment; this led to compulsive lever pressing, whereas depotentiation in persevering mice had the converse effect. In summary, synaptic potentiation of transmission from the OFC to the dorsal striatum drives compulsive reinforcement, a defining symptom of addiction.
PMID: 30568192
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Dataset: https://doi.org/10.5281/zenodo.1474531
Research group Mécanismes cellulaires de la dépendance et de l'addiction (520)
Swiss National Science Foundation: 310030B_170266
Swiss National Science Foundation: 310030B_170266; SYNAPSY; 154737
European Commission: MESSI
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PASCOLI, Vincent Jean et al. Stochastic synaptic plasticity underlying compulsion in a model of addiction. In: Nature, 2018, vol. 564, n° 7736, p. 366-371. doi: 10.1038/s41586-018-0789-4 https://archive-ouverte.unige.ch/unige:118824

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Deposited on : 2019-06-05

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