Desipramine blocks alcohol-induced anxiety- and depressive-like behaviors in two rat strains
Desipramine blocks alcohol-induced anxiety- and depressive-like behaviors in two rat strains
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DOI：
10.1016/j.pbb.2008.06.016
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发表时间：
2008-11-01
影响因子：
3.6
通讯作者：
Tizabi, Yousef
中科院分区：
文献类型：
--
作者：
Getachew, Bruk;Hauser, Sheketha R.;Tizabi, Yousef
流行病学研究表明，酒精中毒，焦虑和抑郁症的显着共病表达。这些症状往往诊断不足，治疗不足，并可能恶化预后和治疗结果的酒精中毒。然而，酗酒和这些疾病之间的因果关系尚未确定。在这项研究中，我们试图确定每天饮酒对两种大鼠品系的焦虑和抑郁指数的影响，其中一种表现出固有的抑郁样特征。此外，研究临床上有用的抗抑郁药对酒精诱导的行为变化的影响也是有意义的。来自Wistar系的Wistar-Kyoto（WKY）大鼠在开放场地中表现出低水平的运动活动，而在强迫游泳试验（FST）中表现出高水平的不动性，该试验被认为是其无助的量度，因此被认为是抑郁症的假定动物模型。将成年雌性WKY和Wistar大鼠每天暴露于95%乙醇蒸汽3小时，以达到约150 mg/dL的平均血液酒精水平（BAL）。将对照暴露于类似吸入室中的空气。在暴露于酒精7或14天后16至18小时，评价开放视野中的自主活动（LCA）、在高架十字迷宫（高架十字迷宫）开放臂中花费的时间、焦虑样行为的反映和FST中的不动性。酒精暴露7或14天，降低LCA只在Wistar大鼠，但增强FST不动性在两个菌株在两个时间点。只有14天的酒精暴露减少了WKY和Wistar大鼠的手臂张开时间。每日治疗与地昔帕明（8毫克/公斤）阻断所有的变化引起的酒精在两个菌株。因此，亚慢性（7天）暴露于酒精诱导抑郁样特征的Wistar大鼠和加重WKY大鼠。然而，慢性（14天）暴露也会在两种菌株中诱导焦虑样效应。酒精引起的抑郁和焦虑样行为可通过三环类抗抑郁药的每日治疗来阻断。这可能表明，预防性治疗酗酒者与抗抑郁药之前，解毒可能会改善治疗结果的酗酒。(c)2008年爱思唯尔公司All rights reserved.
Epidemiological studies indicate significant co-morbid expression of alcoholism, anxiety, and depression. These symptoms are often under-diagnosed and under-treated and can worsen prognostic and treatment outcome for alcoholism. Nonetheless, a causal relationship between alcoholism and these conditions is yet to be established. In this study we sought to determine the effects of daily alcohol administration on the indices of anxiety and depression in two rat strains, one of which exhibits inherent depressive-like characteristics. Moreover, it was of relevance to examine the effects of a clinically useful antidepressant on alcohol-induced behavioral changes. Wistar-Kyoto (WKY) rats derived from Wistar stock show low levels of locomotor activity in an open field and high levels of immobility in the forced swim test (FST) which is considered a measure of their helplessness and hence are considered a putative animal model of depression. Adult female WKY and Wistar rats were exposed for 3 hrs daily to 95% ethanol vapor to achieve a mean blood alcohol level (BAL) of approximately 150 mg/dL. Controls were exposed to air in similar inhalation chambers. Sixteen to 18 hrs following 7 or 14 days of exposure to alcohol, locomotor activity (LCA) in open field, duration of time spent in the open arm of the elevated plus-maze (EPM), reflective of anxiety-like behavior and immobility in FST were evaluated. Alcohol exposure for 7 or 14 days reduced LCA only in Wistar rats but enhanced FST immobility in both strains at both time points. Only 14 day alcohol exposure reduced EPM open arm time in both WKY and Wistar rats. Daily treatment with desipramine (8 mg/kg) blocked all the changes induced by alcohol in both strains. Thus, subchronic (7 day) exposure to alcohol induces depressive-like characteristics in Wistar rats and exacerbates that of WKY rats. Chronic (14 day) exposure, however, also induces an anxiety-like effect in both strains. The depressive- and anxiety-like behaviors induced by alcohol were blocked by daily treatment with a tricyclic antidepressant. It may be suggested that prophylactic treatment of alcoholics with an antidepressant prior to detoxification may improve treatment outcome for alcoholism. (c) 2008 Elsevier Inc. All rights reserved.