Sexually Dimorphic Role for Insular Perineuronal Nets in Aversion-Resistant Ethanol Consumption

Area of Science:

• Neuroscience
• Behavioral Science

Background:

• Compulsive alcohol drinking, a hallmark of alcohol use disorder (AUD), is difficult to treat.
• Perineuroneal nets (PNNs) in the insular cortex modulate aversion-resistant ethanol intake in male mice.
• Female mice exhibit higher aversion-resistant ethanol intake, but the role of PNNs in this behavior is unknown.

Approach:

• Compared PNNs in the insula of male and female mice using Wisteria floribunda agglutinin (WFA) staining.
• Disrupted PNNs in female mice via microinjection of chondroitinase ABC.
• Assessed aversion-resistant ethanol consumption using a two-bottle choice drinking in the dark procedure with quinine.
• Measured insula activation using c-fos immunohistochemistry.

Key Points:

• PNN staining intensity was higher in the insula of female mice compared to males.
• Disrupting PNNs in female mice had a limited effect on aversion-resistant ethanol intake.
• Insula activation during aversion-resistant drinking was lower in female mice than in males.

Conclusions:

• Neural mechanisms underlying aversion-resistant ethanol consumption appear to differ between male and female mice.
• PNNs may not be the primary driver of elevated aversion-resistant drinking in female mice.
• Further research is needed to elucidate sex-specific neurobiological factors in alcohol use disorder.