Addiction Biology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
Basic Clin Pharmacol Toxicol. 2012 Apr;110(4):347-52. doi: 10.1111/j.1742-7843.2011.00819.x. Epub 2011 Nov 9.
Prolonged consumption of ethanol produces prefrontal cortex (PFC) dysfunction in patients, and this has been demonstrated using structural, physiological and psychological measurements. We therefore wanted to develop an animal model of PFC dysfunction to study whether this state changes sensitivity for ethanol or other behavioural/motivational measures. Adolescent Wistar rats were first screened in the novel object recognition task to establish a pre-treatment baseline measure of locomotor activity, anxiety-like behaviour and PFC function. Animals were divided into four treatment groups [saline, 5 mg/kg phencyclidine (PCP), 2.5g/kg ethanol, ethanol + PCP] and injected i.p. for 5 days followed by a 2-day washout. On the 8th day, animals were allowed to explore a Y-maze for 10 min. and spontaneous alternations were recorded using the ANY-maze tracking system. PCP, a classic drug used to induce PFC dysfunction in animals, did not significantly reduce the % correct alternations relative to the 70% level achieved by the saline group. Ethanol and the combination of Ethanol + PCP, however, significantly reduced alternations to approximately 30%. The combined dose was not additive in terms of Y-maze impairment, and these animals had less total distance travelled and greater time immobile relative to the other groups. We therefore concluded that injection of 2.5 g/kg ethanol for 5 days in Wistar rats produces a more substantial, consistent and valid PFC dysfunction than 5 mg/kg PCP.
长期摄入乙醇会导致患者前额叶皮层(PFC)功能障碍,这已通过结构、生理和心理测量得到证实。因此,我们希望开发一种 PFC 功能障碍的动物模型,以研究这种状态是否会改变对乙醇或其他行为/动机措施的敏感性。首先,我们在新颖物体识别任务中筛选了青春期 Wistar 大鼠,以建立运动活动、焦虑样行为和 PFC 功能的预处理基线测量值。动物被分为四组[生理盐水、5mg/kg 苯环利定(PCP)、2.5g/kg 乙醇、乙醇+PCP],并通过腹腔注射连续给药 5 天,然后进行 2 天的洗脱。在第 8 天,动物被允许在 Y 迷宫中探索 10 分钟。使用 ANY-maze 跟踪系统记录自发交替次数。PCP 是一种经典的用于诱导动物 PFC 功能障碍的药物,但与生理盐水组达到的 70%水平相比,它并没有显著降低正确交替的百分比。然而,乙醇和乙醇+PCP 的组合显著降低了交替次数,约为 30%。联合剂量在 Y 迷宫损伤方面没有相加作用,与其他组相比,这些动物的总行进距离更少,静止时间更长。因此,我们得出结论,在 Wistar 大鼠中连续 5 天注射 2.5g/kg 乙醇会导致更显著、一致和有效的 PFC 功能障碍,而不是 5mg/kg PCP。