Davidson M, Wilce P
Department of Biochemistry, The University of Queensland, Australia.
Alcohol Clin Exp Res. 1998 Sep;22(6):1205-11.
Recent research has focused on the N-methyl-D-aspartate receptor system as a major site of ethanol action in the brain and specifically on compensatory changes in the expression of the polyamine-sensitive NR2B subunit. Therefore, we examined the effects of chronic ethanol treatment on polyamine homeostasis in the rat brain. Wistar rats were made dependent by ethanol vapor inhalation. This caused a rise in hippocampal ornithine decarboxylase (ODC) activity that was correlated with the appearance of physiological dependence. ODC activity returned to control levels within 3 days of ethanol withdrawal. Enzyme activity also increased in the cerebral cortex, striatum, and cerebellum of the ethanol-dependent rats. The concentration of the polyamines (putrescine, spermidine, and spermine) in the hippocampus was increased in ethanol-dependent rats. Injection of the ODC inhibitor, alpha-difluoromethylornithine (500 mg/kg) at the onset of withdrawal resulted in a significant reduction in the severity of withdrawal behaviors. The level of ODC activity and the severity of withdrawal behaviors were positively correlated. Perturbed polyamine homeostasis may represent an important molecular component in the initiation of ethanol withdrawal behaviors in the ethanol-dependent rat.
最近的研究聚焦于N-甲基-D-天冬氨酸受体系统，将其作为乙醇在大脑中的主要作用位点，尤其关注对多胺敏感的NR2B亚基表达的代偿性变化。因此，我们研究了慢性乙醇处理对大鼠大脑中多胺稳态的影响。通过吸入乙醇蒸汽使Wistar大鼠产生依赖性。这导致海马鸟氨酸脱羧酶（ODC）活性升高，且与生理依赖性的出现相关。在乙醇戒断3天内，ODC活性恢复至对照水平。乙醇依赖大鼠的大脑皮质、纹状体和小脑中的酶活性也有所增加。乙醇依赖大鼠海马中的多胺（腐胺、亚精胺和精胺）浓度升高。在戒断开始时注射ODC抑制剂α-二氟甲基鸟氨酸（500 mg/kg）可显著减轻戒断行为的严重程度。ODC活性水平与戒断行为的严重程度呈正相关。多胺稳态紊乱可能是乙醇依赖大鼠乙醇戒断行为起始过程中的一个重要分子组成部分。
