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乙醇对雄性和雌性大鼠的镇静及γ-氨基丁酸能作用。

Sedative and GABAergic effects of ethanol on male and female rats.

作者信息

Cha Young May, Li Qiang, Wilson Wilkie A, Swartzwelder H Scott

机构信息

Neurobiology Research Laboratory, Veterans Affairs Medical Center, Durham, North Carolina 27705, USA.

出版信息

Alcohol Clin Exp Res. 2006 Jan;30(1):113-8. doi: 10.1111/j.1530-0277.2006.00005.x.

DOI:10.1111/j.1530-0277.2006.00005.x
PMID:16433738
Abstract

BACKGROUND

Women consume less alcohol than men, and yet they are more susceptible than men to the negative medical consequences of alcohol use, such as cirrhosis of the liver, cardiac disease, and cognitive impairments. This sex difference is also reflected in animal studies, in which male and female rats differ on both behavioral and electrophysiological measures. Given that one significant difference between males and females is the cycling fluctuations of the sex hormones, this study aimed to compare the relative sensitivity of adolescent and adult rats of both sexes and varying estrous stages to the behavioral and electrophysiological effects of ethanol.

METHODS

Adult female rats were lavaged daily for estrous cycle assessment. Following administration of 5 g/kg ethanol, adolescent and adult male and female animals were observed for loss of the righting reflex. Then, using whole-cell recording, we tested the response of spontaneous, gamma-aminobutyric acid (GABA(A)) receptor-mediated inhibitory postsynaptic currents (sIPSCs) in hippocampal slices from drug-naïve adult male and female rats.

RESULTS

Consistent with previous findings, adolescent animals were less sensitive than adults to the effect of ethanol on the righting reflex. In addition, adult proestrous and diestrous female rats were less sensitive than male rats to the sedative effects of ethanol. Finally, ethanol increased the frequency of sIPSCs in hippocampal pyramidal neurons and did so more potently in cells from male rats than in those from female rats.

CONCLUSIONS

Female animals are less sensitive to the behavioral sedative effects of ethanol than adult male rats, and the effect is pronounced in the proestrous and diestrous states. This sex difference may be related to differential sensitivity of GABA receptor-mediated central nervous system function to ethanol in females.

摘要

背景

女性饮酒量低于男性,但她们比男性更容易受到饮酒带来的负面医学后果的影响,如肝硬化、心脏病和认知障碍。这种性别差异在动物研究中也有体现,雄性和雌性大鼠在行为和电生理指标上存在差异。鉴于雄性和雌性之间的一个显著差异是性激素的周期性波动,本研究旨在比较不同性别的青春期和成年大鼠以及不同发情阶段对乙醇行为和电生理效应的相对敏感性。

方法

对成年雌性大鼠每日灌胃以评估发情周期。给予5 g/kg乙醇后,观察青春期和成年雄性及雌性动物的翻正反射消失情况。然后,使用全细胞记录法,测试未接触过药物的成年雄性和雌性大鼠海马切片中自发的、γ-氨基丁酸(GABA(A))受体介导的抑制性突触后电流(sIPSCs)的反应。

结果

与先前的研究结果一致,青春期动物对乙醇对翻正反射的影响比成年动物更不敏感。此外,成年动情前期和动情间期的雌性大鼠对乙醇的镇静作用比雄性大鼠更不敏感。最后,乙醇增加了海马锥体神经元中sIPSCs的频率,并且在雄性大鼠细胞中的作用比雌性大鼠细胞中更显著。

结论

雌性动物对乙醇的行为镇静作用比成年雄性大鼠更不敏感,且在动情前期和动情间期这种作用更为明显。这种性别差异可能与雌性GABA受体介导的中枢神经系统功能对乙醇的不同敏感性有关。

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