Sexually dimorphic role for insular perineuronal nets in aversion-resistant alcohol consumption.
Sexually dimorphic role for insular perineuronal nets in aversion-resistant alcohol consumption.
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DOI：
10.3389/fpsyt.2023.1122423
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发表时间：
2023
影响因子：
4.7
通讯作者：
Lasek, Amy W.
中科院分区：
文献类型：
--
作者：
de Carvalho, Luana Martins;Chen, Hu;Sutter, Mason;Lasek, Amy W.
强迫性饮酒是酒精使用障碍(AUD)的关键症状，尤其对治疗具有抵抗力。了解非强迫性饮酒的生物学因素将有助于开发新的AUD治疗靶点。一种强迫性饮酒的动物模型包括在乙醇溶液中加入苦味奎宁，并测量动物是否愿意饮用酒精，尽管这种味道令人反感。以前的研究表明，这种类型的抗厌恶饮酒在雄性小鼠的岛叶皮质中受到特殊的浓缩细胞外基质的调节，这种细胞外基质被称为神经周围神经网络(PNNS)，它在皮质中表达小白蛋白的神经元周围形成一种晶格状结构。一些实验室已经表明，雌性小鼠表现出更高水平的抗厌恶酒精摄入，但PNNS在雌性小鼠这一行为中的作用尚未得到检验。在这里，我们比较了雄性和雌性小鼠脑岛中的PNNS，并确定干扰雌性小鼠的PNNS是否会改变对厌恶的酒精摄入。用紫藤凝集素(WFA)荧光标记PNNS，并用微量注射软骨素酶ABC(一种消化PNNS中硫酸软骨素糖胺多糖成分的酶)破坏PNNS。通过在黑暗程序中的两瓶选择性饮用中依次增加乙醇中奎宁的浓度，对小鼠进行了抗厌恶乙醇消费的测试。雌性小鼠脑岛的PNN染色强度高于雄性小鼠，提示雌性小鼠PNN可能参与了抗厌恶饮酒能力的增强。然而，中断PNNS对女性抗厌恶饮酒的影响有限。此外，通过c-fos免疫组织化学检测，在抗厌恶饮酒期间，雌性小鼠脑岛的激活程度低于雄性小鼠。综上所述，这些结果表明，男性和女性摄入抗厌恶酒精的神经机制不同。
Compulsive alcohol drinking is a key symptom of alcohol use disorder (AUD) that is particularly resistant to treatment. An understanding of the biological factors that underly compulsive drinking will allow for the development of new therapeutic targets for AUD. 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. 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. 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. 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. 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. 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. 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. However, disruption of PNNs had limited effect on aversion-resistant drinking in females. In addition, activation of the insula during aversion-resistant drinking, as measured by c-fos immunohistochemistry, was lower in female mice than in males. Taken together, these results suggest that neural mechanisms underlying aversion-resistant ethanol consumption differ in males and females.
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