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酒精戒断与酒精依赖动物模型中的阿黑皮素原(POMC)神经肽。

Alcohol Withdrawal and Proopiomelanocortin Neuropeptides in an Animal Model of Alcohol Dependence.

机构信息

Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany.

Departmentof Neurology, Hannover Medical School, Hannover, Germany.

出版信息

Neuropsychobiology. 2019;78(3):118-127. doi: 10.1159/000499844. Epub 2019 May 22.

Abstract

BACKGROUND

Alcohol is one of the leading threats to health worldwide. Craving for alcohol makes abstinence a difficult challenge by maintaining alcohol dependence. Many studies suppose the hypothalamic-pituitary-adrenal axis, especially the proopiomelanocortin (POMC)-derived neuropeptides, to mediate craving during withdrawal in alcohol dependence. Evidence is available that the two POMC proteins, α-melanocyte-stimulating hormone (α-MSH) and β-endorphin (β-END) are altered by alcohol consumption and influence alcohol consumption, respectively.

OBJECTIVES

We investigated the dynamics of α-MSH and β-END during alcohol withdrawal and the influence of intraperitoneal administration of either α-MSH or β-END in an established rodent model (Wistar rats) for alcohol dependence.

RESULTS

After long-term alcohol self-administration over 12 months and repeated deprivation periods for 3 days, we found a significant decrease in α-MSH levels during withdrawal in rodents (p = 0.006) compared to controls, while β-END levels remained unchanged. Treatment with intraperitoneally administered α-MSH and β-END did not affect alcohol drinking behavior after deprivation.

CONCLUSION

We demonstrate the effects of alcohol deprivation on α-MSH in alcohol-dependent rodents, which appear to mimic α-MSH alteration found after fasting periods during appetite regulation. Therefore, low α-MSH levels are a possible indicator for craving in alcohol-dependent individuals and hence would be a potential target for anti-craving treatment.

摘要

背景

酒精是全球范围内对健康的主要威胁之一。对酒精的渴望通过维持酒精依赖使戒酒成为一项艰巨的挑战。许多研究假设,下丘脑-垂体-肾上腺轴,特别是前阿黑皮素原(POMC)衍生的神经肽,在酒精依赖戒断期间介导对酒精的渴望。有证据表明,两种 POMC 蛋白,α-黑素细胞刺激素(α-MSH)和β-内啡肽(β-END)分别受到酒精摄入的影响并影响酒精摄入。

目的

我们研究了 POMC 衍生的神经肽在酒精戒断期间的动态变化,以及在建立的酒精依赖啮齿动物模型(Wistar 大鼠)中腹腔内给予 α-MSH 或 β-END 对其的影响。

结果

在长达 12 个月的长期酒精自我给药和 3 天的重复剥夺期后,我们发现与对照组相比,在戒断期间啮齿动物的 α-MSH 水平显著降低(p = 0.006),而 β-END 水平保持不变。腹腔内给予 α-MSH 和 β-END 治疗并未影响剥夺后的酒精饮用量。

结论

我们证明了酒精剥夺对酒精依赖啮齿动物中 α-MSH 的影响,这似乎模拟了在食欲调节期间禁食期间发现的 α-MSH 改变。因此,低 α-MSH 水平可能是酒精依赖个体渴望的一个可能指标,因此可能成为抗渴望治疗的潜在靶点。

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