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青春期间歇性乙醇暴露对雄性和雌性大鼠社交性饮酒行为和神经肽基因表达的影响。

Impact of adolescent intermittent ethanol exposure in male and female rats on social drinking and neuropeptide gene expression.

机构信息

Neurobiology of Adolescent Drinking in Adulthood Consortium, Center for Development and Behavioral Neuroscience, Department of Psychology, Binghamton University, Binghamton, New York, USA.

出版信息

Alcohol Clin Exp Res. 2022 Jun;46(6):979-993. doi: 10.1111/acer.14847. Epub 2022 May 2.

Abstract

BACKGROUND

Alcohol use during adolescence can alter maturational changes that occur in brain regions associated with social and emotional responding. Our previous studies have shown that adult male, but not female rats demonstrate social anxiety-like alterations and enhanced sensitivity to ethanol-induced social facilitation following adolescent intermittent ethanol exposure (AIE). These consequences of AIE may influence adult social drinking in a sex-specific manner.

METHODS

To test the effects of AIE on social drinking, male and female Sprague-Dawley rats exposed to water or ethanol (0 or 4 g/kg, intragastrically, every other day, between postnatal day [P] 25 and 45) were tested as adults (P72-83) in a social drinking paradigm (30-minute access to a 10% ethanol solution in supersac or supersac alone in groups of three same-sex littermates across two 4-day cycles separated by 4 days off). Social behavior was assessed during the last drinking session, along with assessment of oxytocin (OXT), oxytocin receptor (OXTR), vasopressin (AVP), and vasopressin receptors 1a and 1b (AVPR1a, AVPR1b) in the hypothalamus and lateral septum.

RESULTS

Males exposed to AIE consumed more ethanol than water-exposed controls during the second drinking cycle, whereas AIE did not affect supersac intake in males. AIE-exposed females consumed less ethanol and more supersac than water-exposed controls. Water-exposed females drinking ethanol showed more social investigation and significantly higher hypothalamic OXTR, AVP, and AVPR1b gene expression than their counterparts ingesting supersac and AIE females drinking ethanol. In males, hypothalamic AVPR1b gene expression was affected by drinking solution, with significantly higher expression evident in males drinking ethanol than those consuming supersac.

CONCLUSIONS

Collectively, these findings provide new evidence regarding sex-specific effects of AIE on social drinking and suggest that the hypothalamic OXT and AVP systems are implicated in the effects of ingested ethanol on social behavior in a sex- and adolescent-exposure-dependent manner.

摘要

背景

青春期饮酒会改变与社交和情绪反应相关的大脑区域的成熟变化。我们之前的研究表明,成年雄性大鼠而非雌性大鼠在经历青春期间歇性乙醇暴露(AIE)后表现出类似社交焦虑的改变和对乙醇诱导的社交促进作用更为敏感。这些 AIE 的后果可能以性别特异性的方式影响成年社交性饮酒。

方法

为了测试 AIE 对社交性饮酒的影响,雄性和雌性 Sprague-Dawley 大鼠在出生后第 25 天至 45 天期间,每天两次接受水或乙醇(0 或 4 g/kg,灌胃)暴露,然后在成年期(P72-83)进行社交性饮酒范式测试(在两个 4 天的间歇期之间,三组同性别同窝仔鼠在 30 分钟内可接触 10%乙醇溶液或单独接触 Supersac)。在最后一次饮酒期间评估社交行为,同时评估下丘脑和外侧隔室中的催产素(OXT)、催产素受体(OXTR)、血管加压素(AVP)和血管加压素受体 1a 和 1b(AVPR1a、AVPR1b)。

结果

暴露于 AIE 的雄性大鼠在第二个饮酒周期中比暴露于水的对照组消耗更多的乙醇,而 AIE 对雄性大鼠的 Supersac 摄入量没有影响。暴露于 AIE 的雌性大鼠比暴露于水的对照组消耗更少的乙醇和更多的 Supersac。摄入乙醇的水暴露雌性大鼠比摄入 Supersac 的水暴露对照组和摄入乙醇的 AIE 雌性大鼠表现出更多的社交探索,并且下丘脑 OXTR、AVP 和 AVPR1b 基因表达显著升高。在雄性大鼠中,下丘脑 AVPR1b 基因表达受饮液影响,摄入乙醇的雄性大鼠的表达明显高于摄入 Supersac 的雄性大鼠。

结论

总的来说,这些发现为 AIE 对社交性饮酒的性别特异性影响提供了新的证据,并表明下丘脑的 OXT 和 AVP 系统参与了摄入的乙醇对社交行为的影响,这种影响具有性别和青春期暴露依赖性。

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