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大鼠基础前脉冲抑制水平与乙醇戒断严重程度的关系。

The relationship between baseline prepulse inhibition levels and ethanol withdrawal severity in rats.

机构信息

Department of Medical Pharmacology, Psychopharmacology Research Unit, Gulhane Military Medical Academy, Ankara, Turkey.

出版信息

Prog Neuropsychopharmacol Biol Psychiatry. 2010 Dec 1;34(8):1507-14. doi: 10.1016/j.pnpbp.2010.08.014. Epub 2010 Aug 26.

Abstract

Baseline prepulse inhibition (PPI) of the acoustic startle reflex is thought to reflect the functioning of the sensorimotor gating system in the brain. The current literature indicates that similar neurotransmitter systems may play roles both in the regulation of PPI and in the development of ethanol withdrawal syndrome (EWS). The aim of the present study was to test if individual baseline PPI levels have any relationship to the behavioral and neurochemical consequences of EWS in rats. A batch of rats (n=30) was sorted according to baseline PPI levels and classified as either high-inhibitory (HI) or low-inhibitory (LI) rats (n=10 in each group). Ethanol was administered in a liquid diet for 21 days. On the 22nd day, ethanol was removed from the diet, and EWS was induced. At the 2nd, 4th, and 6th hours of EWS, locomotor activity and behavioral symptoms were evaluated. Brain tissue concentrations of dopamine, serotonin and noradrenaline in hippocampus, cortex, and striatum were measured after the 6th hour of EWS testing. Another batch of rats (n=30) was classified using the same procedure and fed with regular diet. On the 22nd day, rats were decapitated and neurochemical measurements were repeated. HI and LI rats consumed similar amounts of ethanol. However, EWS signs such as stereotyped behaviors, wet-dog shakes, and tremor were more intense in LI rats compared to their HI counterparts. Audiogenic seizures occurred in both groups in a similar manner. Although the catecholamine concentrations in the brains of both groups were parallel under baseline conditions, dopamine levels increased in the cortex of LI and in the striatum of HI rats, whereas striatum serotonin levels decreased only in LI rats after the 6th hour of EWS. In conclusion, the data suggest that the behavioral symptoms and neurochemical changes observed in EWS may be associated with baseline PPI levels.

摘要

基础预备性惊吓反射(PPI)被认为反映了大脑中感觉运动门控系统的功能。目前的文献表明,相似的神经递质系统可能在 PPI 的调节和乙醇戒断综合征(EWS)的发展中发挥作用。本研究的目的是测试个体基础 PPI 水平是否与 EWS 对大鼠的行为和神经化学后果有关。一批大鼠(n=30)根据基础 PPI 水平进行分类,并分为高抑制(HI)或低抑制(LI)大鼠(每组 10 只)。用液体饮食给大鼠连续 21 天灌胃乙醇。第 22 天,从饮食中去除乙醇,诱导 EWS。在 EWS 的第 2、4 和 6 小时,评估运动活动和行为症状。在 EWS 测试的第 6 小时后,测量海马、皮质和纹状体中多巴胺、血清素和去甲肾上腺素的脑浓度。另一批大鼠(n=30)按照相同的程序进行分类,并给予常规饮食。第 22 天,大鼠断头并重复神经化学测量。HI 和 LI 大鼠摄入的乙醇量相似。然而,LI 大鼠比其 HI 对应物表现出更强烈的 EWS 症状,如刻板行为、湿狗抖动和震颤。两组均以相似的方式发生听觉性癫痫发作。尽管两组大鼠的基础条件下儿茶酚胺浓度平行,但 LI 大鼠的皮质和 HI 大鼠的纹状体中多巴胺水平增加,而只有 LI 大鼠的纹状体血清素水平在 EWS 后的第 6 小时下降。总之,数据表明,EWS 中观察到的行为症状和神经化学变化可能与基础 PPI 水平有关。

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