Sahr A E, Thielen R J, Lumeng L, Li T-K, McBride W J
Graduate Program in Medical Neurobiology, Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indiana University-Purdue University at Indianapolis, Indianapolis, Indiana, USA.
Alcohol Clin Exp Res. 2004 May;28(5):702-11. doi: 10.1097/01.alc.0000125344.79677.1c.
This study tested the hypothesis that ethanol consumption by alcohol-preferring (P) rats during the periadolescent period causes persistent alterations in the mesolimbic dopamine (DA) system. After ethanol drinking during periadolescence, P rats were examined for alterations in basal locomotor activity, changes in extracellular DA levels and extraction fraction in the nucleus accumbens (NAc) by using no-net-flux (NNF) microdialysis, and changes in the response of the mesolimbic DA system to ethanol.
Male P rat pups were given 24-hr free-choice access to 15% (v/v) ethanol from postnatal day (PD) 30 through PD 60. On PD 70, rats were assessed for locomotor activity. On PD 70 to 80, rats were implanted with bilateral guide cannulas aimed above the NAc. After at least 5 days, microdialysis probes were inserted bilaterally; on the following day, NNF microdialysis experiments were conducted. On the day after the NNF experiment, conventional microdialysis experiments were conducted to measure extracellular levels of DA in response to intraperitoneal injection of saline or ethanol 2.5 g/kg.
Compared with the ethanol-naive group, ethanol drinking by P rats during periadolescence did not alter basal locomotor activity, nor did it alter the basal extracellular concentration of DA. There was, however, a significant increase in the extraction fraction of DA of ethanol-drinking animals relative to the controls (57.4 +/- 2.7% and 45.8 +/- 2.3%, respectively). Additionally, compared with controls, P rats with exposure to ethanol during the periadolescent period showed a prolonged increase in the extracellular levels of DA after a challenge dose of ethanol.
The results of the microdialysis experiments suggest that periadolescent ethanol drinking by P rats increases basal DA neurotransmission (as indicated by higher DA clearance while maintaining the same extracellular DA concentrations) and prolongs the response of DA neurotransmission to ethanol.
本研究检验了以下假设：偏爱酒精的（P）大鼠在青春期前后摄入乙醇会导致中脑边缘多巴胺（DA）系统发生持续性改变。在青春期前后饮用乙醇后，对P大鼠进行基础运动活动改变、伏隔核（NAc）细胞外DA水平变化以及利用无净通量（NNF）微透析法测定提取分数的检查，并观察中脑边缘DA系统对乙醇反应的变化。
雄性P大鼠幼崽从出生后第30天（PD）至第60天可自由选择饮用24小时的15%（v/v）乙醇。在PD 70时，评估大鼠的运动活动。在PD 70至80时，给大鼠双侧植入瞄准NAc上方的引导套管。至少5天后，双侧插入微透析探针；次日，进行NNF微透析实验。在NNF实验后的第二天，进行传统微透析实验，以测量腹腔注射生理盐水或2.5 g/kg乙醇后DA的细胞外水平。
与未接触乙醇的组相比，P大鼠在青春期前后饮用乙醇并未改变基础运动活动，也未改变DA的基础细胞外浓度。然而，与对照组相比，饮用乙醇的动物DA的提取分数显著增加（分别为57.4±2.7%和45.8±2.3%）。此外，与对照组相比，在青春期前后接触乙醇的P大鼠在给予乙醇激发剂量后，DA的细胞外水平升高的持续时间延长。
微透析实验结果表明，P大鼠在青春期前后饮用乙醇会增加基础DA神经传递（如在保持相同细胞外DA浓度的情况下，DA清除率更高所示），并延长DA神经传递对乙醇的反应。
