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bioRxiv · 10.1101/504571

Perineuronal Nets in the Insula Regulate Aversion-Resistant Alcohol Drinking

Chen, H.·Lasek, A. W.
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Abstract

One of the most pernicious characteristics of alcohol use disorder is the compulsion to drink despite negative consequences. The insular cortex (insula) controls decision-making under conditions of risk or conflict and regulates maladaptive behaviors in the context of addiction. Cortical activity is tightly controlled by fast-spiking inhibitory interneurons that are often enclosed by specialized extracellular matrix structures known as perineuronal nets, which regulate neuronal excitability and plasticity. Using a mouse model of compulsive drinking in which alcohol was adulterated with the bitter tastant quinine, we demonstrate that disrupting perineuronal nets in the insula rendered mice more sensitive to quinine-adulterated alcohol. Activation of the insula, as measured by c-fos expression, occurred during aversion-resistant drinking and was further enhanced by elimination of perineuronal nets. These results provide fundamental insight into neuroanatomical and cellular mechanisms that control compulsive drinking.

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Chen, H., Lasek, A. W.. 2018-12-21. Perineuronal Nets in the Insula Regulate Aversion-Resistant Alcohol Drinking. https://doi.org/10.1101/504571

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