Clinical Research Institute, Seoul National University Hospital, 101 Daehak-Ro, Jongno-Gu, Seoul 110-744, Republic of Korea; Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Seoul 110-744, Republic of Korea.
Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Seoul 110-744, Republic of Korea; Department of Psychiatry and Behavioral Science, Seoul National University, College of Medicine, 101 Daehak-Ro, Jongno-Gu, Seoul 110-744, Republic of Korea.
Pharmacol Biochem Behav. 2017 Sep;160:47-54. doi: 10.1016/j.pbb.2017.08.001. Epub 2017 Aug 10.
Repeated exposure to drugs of abuse can induce a progressive increase in locomotor activity, known as behavioral sensitization. However, little is known about behavioral sensitization to ethanol. We examined whether ethanol could induce behavioral sensitization and investigated several molecular changes accompanying sensitization. We also assessed whether "cross-sensitization" occurred between ethanol and cocaine, another abused drug. Ethanol-induced sensitization was examined in rats after ethanol treatment (0.5 or 2g/kg) for 15days. The biochemical effects of low- or high-dose ethanol were examined in terms of N-methyl-d-aspartate (NMDA) receptor subunit phosphorylation or expression. Neuronal activity after ethanol treatment was assessed by measuring the level of early growth response (Egr-1) expression. Ethanol-induced behavioral sensitization was observed at the low dose (0.5g/kg) but not the high dose (2g/kg). Although acute treatment with the sensitizing dose of ethanol robustly increased Egr-1 protein and mRNA levels, the expression and phosphorylation of NMDA receptor subunits were not affected. The biochemical responses to ethanol seemed to be enhanced in ethanol-sensitized animals. Cross-sensitization between ethanol and cocaine was observed, which supports the hypothesis that there are commonalities among substances in the pathophysiology of substance dependence.
反复接触滥用药物会导致运动活动的逐渐增加，称为行为敏化。然而，对于乙醇的行为敏化知之甚少。我们研究了乙醇是否可以引起行为敏化，并研究了伴随敏化的几种分子变化。我们还评估了乙醇和另一种滥用药物可卡因之间是否发生“交叉敏化”。在大鼠中，用乙醇（0.5 或 2g/kg）处理 15 天后，检查了乙醇诱导的敏化作用。用 N-甲基-D-天冬氨酸（NMDA）受体亚基磷酸化或表达来检查低剂量或高剂量乙醇的生化作用。通过测量早期生长反应（Egr-1）表达水平来评估乙醇处理后的神经元活性。在低剂量（0.5g/kg）而不是高剂量（2g/kg）下观察到乙醇诱导的行为敏化。尽管用敏化剂量的乙醇急性处理可强烈增加 Egr-1 蛋白和 mRNA 水平，但 NMDA 受体亚基的表达和磷酸化不受影响。乙醇敏化动物的生化反应似乎增强了。在乙醇和可卡因之间观察到交叉敏化，这支持了物质依赖的病理生理学中存在物质共性的假说。
