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bioRxiv · 10.1101/471847

Single-cell whole-brain imaging and network analysis provide evidence of the three-stage hypothesis of addiction

Kimbrough, A.·Lurie, D. J.·Collazo, A.·Kreifeldt, M.·Sidhu, H.·D'Esposito, M.·Contet, C.·George, O.
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Abstract

Three main theories of the neurobiology of addiction have been proposed: (1) incentive salience mediated by a brainstem-striatal network, (2) habit mediated by a cortico-striato-thalamic network, and (3) hedonic allostasis mediated by an extended amygdala network. Efforts have been made to reconcile these theories within a three-stage model, but the relevance of each theory remains controversial. We tested the validity of each theory with a single dataset using unbiased single-cell whole-brain imaging and data-driven analyses of neuronal activity in a mouse model of alcohol use disorder. Abstinence in alcohol dependent mice decreased brain modularity and resulted in clustering of brain regions that correspond to each stage of the three-stage theory of addiction. Furthermore, we identified several brain regions whose activity highly predicted addiction-like behaviors and \"hub\" regions that may drive neural activation during abstinence. These results validate the three-stage theory of addiction and identify potential target regions for future study.

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Kimbrough, A., Lurie, D. J., Collazo, A., Kreifeldt, M., Sidhu, H., D'Esposito, M., Contet, C., George, O.. 2018-11-21. Single-cell whole-brain imaging and network analysis provide evidence of the three-stage hypothesis of addiction. https://doi.org/10.1101/471847

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