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左乙拉西坦和乙醇对大鼠记忆、部分神经递质水平、氧化应激参数和必需元素的影响。

Impact of levetiracetam and ethanol on memory, selected neurotransmitter levels, oxidative stress parameters, and essential elements in rats.

机构信息

Department of Pharmacodynamics, Medical University of Lodz, Muszyńskiego 1, Łódź, 90-151, Poland.

Department of Toxicology, Medical University of Lodz, Muszyńskiego 1, Łódź, 90-151, Poland.

出版信息

Pharmacol Rep. 2024 Dec;76(6):1363-1376. doi: 10.1007/s43440-024-00659-5. Epub 2024 Oct 1.

Abstract

BACKGROUND

Ethanol disrupts brain activity and memory. There is evidence supporting the beneficial effect of levetiracetam on alcohol consumption. Therefore, the aim of the study was to examine whether levetiracetam has a protective activity against ethanol-induced memory impairment, alterations in selected neurotransmission activities, oxidative stress, and selected essential elements in rats.

METHODS

The rats were given levetiracetam (300 mg/kg b.w. po) with ethanol for three weeks prior to behavioral tests. Spatial memory was tested using the Morris water maze, while recognition memory was evaluated using the Novel object recognition test. The GABA and glutamate concentration was determined in three rat brain regions (cerebellum, hippocampus, and cerebral cortex). Serum oxidative stress parameters and selected essential elements concentration (Cu, Mn, Zn, Fe, Mg) in the rat brain were analyzed.

RESULTS

Levetiracetam administered with ethanol improved spatial memory, but did not affect abstinence-induced impairment. The drug also decreased ethanol-induced long-term recognition memory impairment. No alterations in glutamate levels were observed. GABA levels were elevated by levetiracetam in the cerebral cortex and by ethanol in the cerebellum. Ethanol increased catalase activity (CAT) and decreased superoxide dismutase activity (SOD) in the serum. Levetiracetam significantly increased the activity of SOD. Alcohol disrupted the levels of trace elements (Mn, Zn, Mg) in the rat brain. Additionally, levetiracetam alone increased Mg, Fe, and Cu concentrations while all animals receiving the drug also had significantly lower concentrations of Zn.

CONCLUSIONS

Levetiracetam had differential effects against ethanol-induced impairments. These findings could have important implications for future levetiracetam treatment in patients.

摘要

背景

乙醇会破坏大脑活动和记忆。有证据表明,左乙拉西坦对饮酒有有益的影响。因此,本研究的目的是研究左乙拉西坦是否对乙醇诱导的记忆损伤、某些神经递质活性的改变、氧化应激和大鼠某些必需元素具有保护作用。

方法

在进行行为测试之前,大鼠给予左乙拉西坦(300mg/kg 体重,po)和乙醇,共三周。空间记忆通过 Morris 水迷宫测试,而识别记忆通过新物体识别测试进行评估。测定了三个大鼠脑区(小脑、海马和大脑皮层)中的 GABA 和谷氨酸浓度。分析了大鼠血清氧化应激参数和某些必需元素浓度(Cu、Mn、Zn、Fe、Mg)。

结果

左乙拉西坦与乙醇联合使用可改善空间记忆,但不影响戒断引起的损伤。该药物还可减轻乙醇引起的长期识别记忆损伤。未观察到谷氨酸水平的改变。左乙拉西坦可增加大脑皮层中的 GABA 水平,乙醇可增加小脑中的 GABA 水平。乙醇增加了血清中的过氧化氢酶(CAT)活性,降低了超氧化物歧化酶(SOD)活性。左乙拉西坦可显著增加 SOD 活性。酒精破坏了大鼠脑内微量元素(Mn、Zn、Mg)的水平。此外,左乙拉西坦单独使用可增加 Mg、Fe 和 Cu 的浓度,而所有接受该药物的动物的 Zn 浓度也显著降低。

结论

左乙拉西坦对乙醇诱导的损伤具有不同的作用。这些发现可能对未来左乙拉西坦治疗患者具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd17/11582331/3c18af22ed37/43440_2024_659_Fig1_HTML.jpg

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