![]() Clinical and preclinical studies have demonstrated sex differences during different stages of the addiction cycle ( 3) and suggest that hormonal and genetic factors are involved in sex differences in addiction ( 4). Socioeconomic factors can account for some of this increase, but biological factors also play a role in the initiation of alcohol use and progression to AUD ( 2). ![]() From 2002 to 2012, AUD diagnosis in women increased by 83.7% ( 1). Although more men than women have historically been diagnosed with AUD, the prevalence of this disorder in women has increased in recent decades. Taken together, these results suggest that neural mechanisms underlying aversion-resistant ethanol consumption differ in males and females.Īlcohol use disorder (AUD) is characterized by the inability to stop or limit alcohol use despite adverse effects on one’s health, relationships, and occupation. In addition, activation of the insula during aversion-resistant drinking, as measured by c-fos immunohistochemistry, was lower in female mice than in males. However, disruption of PNNs had limited effect on aversion-resistant drinking in females. PNN staining intensity was higher in the insula of female compared to male mice, suggesting that PNNs in females might contribute to elevated aversion-resistant drinking. Mice were tested for aversion-resistant ethanol consumption by the addition of sequentially increasing concentrations of quinine to the ethanol in a two-bottle choice drinking in the dark procedure. PNNs were visualized in the insula by fluorescent labeling with Wisteria floribunda agglutinin (WFA) and disrupted in the insula by microinjecting chondroitinase ABC, an enzyme that digests the chondroitin sulfate glycosaminoglycan component of PNNs. Here we compared PNNs in the insula of male and female mice and determined if disrupting PNNs in female mice would alter aversion-resistant ethanol intake. Several laboratories have shown that female mice exhibit higher levels of aversion-resistant ethanol intake, but the role of PNNs in females in this behavior has not been examined. Previous studies have demonstrated that this type of aversion-resistant drinking is modulated in the insular cortex of male mice by specialized condensed extracellular matrix known as perineuronal nets (PNNs), which form a lattice-like structure around parvalbumin-expressing neurons in the cortex. One animal model of compulsive alcohol drinking involves the addition of bitter-tasting quinine to an ethanol solution and measuring the willingness of the animal to consume ethanol despite the aversive taste. An understanding of the biological factors that underly compulsive drinking will allow for the development of new therapeutic targets for AUD. Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois Chicago, Chicago, IL, United StatesĬompulsive alcohol drinking is a key symptom of alcohol use disorder (AUD) that is particularly resistant to treatment. ![]() ![]() Luana Martins de Carvalho †, Hu Chen, Mason Sutter and Amy W. ![]()
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