Alcohol withdrawal increases neuropeptide Y immunoreactivity in rat brain
Alcohol withdrawal increases neuropeptide Y immunoreactivity in rat brain
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DOI：
10.1097/01.alc.0000075827.74538.fe
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发表时间：
2003-07-01
影响因子：
3.2
通讯作者：
Crews, F
中科院分区：
文献类型：
--
作者：
Bison, S;Crews, F
背景资料：神经肽Y（NPY）在大脑中广泛表达，已知其影响包括饮酒在内的消费行为，并在癫痫发作中发挥作用。我们研究了一个4天的酒精狂欢治疗模型的影响，该模型已知会诱导身体依赖和戒断癫痫发作，以确定酒精依赖和戒断对NPY表达的影响。雄性Sprague道利（R）大鼠用乙醇或对照营养完全饮食通过每天三次胃内处理进行处理，持续2或4天，平均日剂量为约8 g/kg。kg乙醇。还研究了给药4天然后停药24、72和168小时的乙醇喂养大鼠。脑灌注和切片的NPY，磷酸环腺苷反应元件结合（pCREB），和其他protein.Results免疫组化：NPY免疫反应（NPY-IR）被发现在几个脑区，海马和大脑皮层表现出最明显的变化。NPY-IR减少乙醇处理的海马和皮质，虽然在72小时的撤退有一个显着增加，在门的齿状回和海马CA 3和CA 2领域的NPY-IR。乙醇戒断癫痫发作发生在12至24小时左右的撤退，在NPY-IR的变化在72小时之前。pCREB免疫反应性（pCREB-IR）在乙醇处理过程中趋于减少，但在72小时的撤退齿状回显着增加。小清蛋白免疫反应表明，一些pCREB-IR和NPY-IR的抑制性中间神经元篮细胞的海马门。NPY-IR恢复到控制水平的168小时withdraw.Conclusions：这些研究表明，海马神经肽Y减少乙醇依赖的发展过程中。乙醇戒断性癫痫发作先于海马神经肽Y免疫反应的显著增加。以往的研究表明，海马神经肽Y减少癫痫发作活动，并且神经肽Y是由癫痫发作活动诱导的。因此，在72小时的戒断酒精治疗后，在NPY-IR的增加可能是对长期的戒断发作活动的保护。
Background: Neuropeptide Y (NPY) is widely expressed in the brain and is known to affect consummatory behaviors including drinking alcohol as well as to play a role in seizures. We investigated the effects of a 4 day binge ethanol treatment model that is known to induce physical dependence and withdrawal seizures to determine the effects of ethanol dependence and withdrawal on NPY expression.Methods: Male Sprague Dawley(R) rats were treated with ethanol or control nutritionally complete diets by intragastric treatment three times per day for 2 or 4 days with an average daily dose of approximately 8 g/kg ethanol per day. Ethanol-fed rats treated for 4 days and then withdrawn for 24, 72, and 168 hr also were studied. Brains were perfused and sectioned for immumohistochemistry for NPY, phospho-cyclic adenosine monophosphate responsive element binding (pCREB), and other proteins.Results: NPY immunoreactivity (NPY-IR) was found in several brain regions, with the hippocampus and cerebral cortex showing the most pronounced changes. NPY-IR was reduced by ethanol treatment in hippocampus and cortex, although at 72 hr of withdrawal there was a dramatic increase in NPY-IR in the hilus of the dentate gyrus and in CA3 and CA2 fields of hippocampus. Ethanol withdrawal seizures occurred around 12 to 24 hr of withdrawal, preceding the changes in NPY-IR at 72 hr. pCREB immunoreactivity (pCREB-IR) tended to decrease during ethanol treatment but showed a dramatic increase in dentate gyrus at 72 hr of withdrawal. Parvalbumin immunoreactivity indicated that some of the pCREB-IR and NPY-IR were within inhibitory interneuron basket cells of the hippocampal hilus. NPY-IR returned to control levels by 168 hr of withdrawal.Conclusions: These studies suggest that hippocampal NPY is reduced during the development of ethanol dependence. Ethanol withdrawal seizures precede a dramatic increase in hippocampal NPY-IR. Previous studies have suggested that NPY in the hippocampus reduces seizure activity and that NPY is induced by seizure activity. Thus, the increase in NPY-IR at 72 hr of withdrawal after binge ethanol treatment may be protective against prolonged withdrawal seizure activity.