Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany.
Departmentof Neurology, Hannover Medical School, Hannover, Germany.
Neuropsychobiology. 2019;78(3):118-127. doi: 10.1159/000499844. Epub 2019 May 22.
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.
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.
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.
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.
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。
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。
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。
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。