Decreased reward during acute alcohol withdrawal in rats selectively bred for low alcohol drinking
Decreased reward during acute alcohol withdrawal in rats selectively bred for low alcohol drinking
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DOI：
10.1016/j.alcohol.2006.06.009
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发表时间：
2006-04-01
期刊：
影响因子：
2.3
通讯作者：
Froehlich, Janice C.
中科院分区：
文献类型：
--
作者：
Chester, Julia A.;Rausch, Edward J.;Froehlich, Janice C.
我们以前曾假设，增加敏感性的抑郁样或厌恶的影响，酒精戒断后，最初暴露于酒精可能与遗传倾向，以避免酒精。通过颅内自我刺激（ICSS）奖励阈值升高测量的脑奖励功能降低是少数几种可用于模拟大鼠中药物戒断的抑郁样或厌恶效应的方法之一。我们比较了大脑的奖励功能，在撤回后，首次暴露于酒精的酒精幼稚大鼠选择性地培育高（HAD 1线）与低（LAD 1线）自愿饮酒。雄性HAD 1（n = 5）和LAD 1（n = 6）大鼠在内侧前脑束中植入单侧电极，并训练棒压以递送频率从45至200 Hz变化的100 μ A电流。在给定日期的多个实验阶段以及在酒精或水给药前的连续几天，受试者的ICSS应答通常稳定。在单次胃内注入酒精（4.0 g/kg体重）或水之前和之后12、14、16、18、20和24 h，在两种大鼠系中评估ICSS反应。LAD 1系大鼠（而非HAD 1系大鼠）表现出大脑奖赏功能的降低，这一点可通过酒精戒断期间ICSS的压杆反应降低和ICSS刺激阈值增加来证明。研究结果表明，大鼠选择性饲养的低酒精饮用可能会经历抑郁样的影响，从最初暴露于酒精退出，而大鼠选择性饲养的高酒精饮用可能不会。(c)2006爱思唯尔公司All rights reserved.
We have previously hypothesized that increased sensitivity to the dysphoric-like or aversive effects of alcohol withdrawal following an initial exposure to alcohol might be associated with a genetic propensity to avoid alcohol. A decrease in brain reward function, as measured by an elevation in intracranial self-stimulation (ICSS) reward threshold, is one of the few methods available to model dysphoric-like or aversive effects of drug withdrawal in rats. We compared brain reward function during withdrawal following an initial exposure to alcohol in alcohol-naive rats selectively bred for high (HAD1 line) versus low (LAD1 line) voluntary alcohol consumption. Male HAD1 (n = 5) and LAD1 (n = 6) rats were implanted with unilateral electrodes in the medial forebrain bundle and trained to bar press for delivery of a 100 mu A current that varied in frequency from 45 to 200 Hz. Responding for ICSS was generally stable within subjects across multiple experimental sessions on a given day and across several consecutive days prior to alcohol or water administration. ICSS responding was assessed in both rat lines prior to and at 12, 14, 16, 18, 20, and 24 h following a single intragastric infusion of alcohol (4.0 g/kg body weight) or water. Rats of the LAD1 line, but not those of the HAD1 line, exhibited a decrease in brain reward function as evidenced by a decrease in bar-press responding for ICSS and an increase in ICSS stimulation threshold during alcohol withdrawal. The results suggest that rats selectively bred for low alcohol drinking may experience dysphoric-like effects during withdrawal from an initial exposure to alcohol, while rats selectively bred for high alcohol drinking may not. (c) 2006 Elsevier Inc. All rights reserved.