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Perineuronal nets in the insula regulate aversion-resistant alcohol drinking.

Hu Chen1, Amy W Lasek1

  • 1Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA.

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|August 22, 2019
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Summary
This summary is machine-generated.

Perineuronal nets (PNNs) in the insula regulate aversion-resistant alcohol drinking. Disrupting these nets increases sensitivity to alcohol adulterated with bitter substances, suggesting a novel therapeutic target.

Keywords:
alcoholaversioncompulsive drinkingethanolextracellular matrixinsulaperineuronal nets

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Area of Science:

  • Neuroscience
  • Addiction Research
  • Molecular and Cellular Biology

Background:

  • Alcohol use disorder is characterized by compulsive drinking despite negative consequences.
  • The insular cortex is crucial for decision-making in conflict situations.
  • Perineuronal nets (PNNs) regulate neuronal activity and plasticity, particularly in inhibitory interneurons.

Purpose of the Study:

  • To investigate the role of insular PNNs in aversion-resistant alcohol drinking.
  • To determine if PNNs modulate the insula's response during compulsive alcohol consumption.

Main Methods:

  • Utilized a mouse model where ethanol was mixed with quinine (a bitter substance).
  • Manipulated PNNs in the insula to assess their effect on drinking behavior.
  • Measured insula activation using c-fos expression as an indicator.

Main Results:

  • Disrupting insular PNNs increased sensitivity to quinine-adulterated ethanol, but not ethanol alone.
  • Insular activation was observed during aversion-resistant drinking.
  • Eliminating PNNs further enhanced insular activation during this behavior.

Conclusions:

  • PNNs in the insula play a critical role in controlling neural activation during aversion-resistant alcohol drinking.
  • Maintaining excitatory/inhibitory balance within the insula is vital for conflict-driven decision-making.
  • Targeting insular PNNs or modulating insula activation presents a potential strategy for reducing compulsive alcohol use.