Anxiety and depression are symptoms associated with ethanol withdrawal that lead individuals to relapse. In the kynurenine pathway, the enzyme indoleamine 2,3 dioxygenase (IDO) is responsible for the conversion of tryptophan to kynurenine, and dysregulation of this pathway has been associated with psychiatric disorders, such as anxiety and depression. The present study evaluated the early and late behavioral and biochemical effects of ethanol withdrawal in rats. Male Wistar rats were submitted to increasing concentrations of ethanol in drinking water during 21 days. In experiment 1, both control and withdrawal groups were submitted to a battery of behavioral tests 3, 5, 10, 19, and 21 days following ethanol removal. In experiment 2, animals were euthanized 3 days (short-term) or 21 days (long-term) after withdrawal, and the brains were dissected altogether, following kynurenine concentration analysis in prefrontal cortex, hippocampus, and striatum. Short-term ethanol withdrawal decreased the exploration of the open arms in the elevated plus-maze. In the forced swimming test, long-term ethanol-withdrawn rats displayed higher immobility time than control animals. Ethanol withdrawal altered neither locomotion nor motor coordination of rats. In experiment 2, kynurenine concentrations were increased in the prefrontal cortex after a long-term period of withdrawal. In conclusion, short-term ethanol withdrawal produced anxiety-like behaviors, while long-term withdrawal favored depressive-like behaviors. Long-term ethanol withdrawal elevated kynurenine levels, specifically in the prefrontal cortex, suggesting that the depressive-like responses observed after long-term withdrawal might be related to the increased IDO activity.

焦虑和抑郁是与乙醇戒断相关的症状，导致个体复发。在犬尿氨酸途径中，吲哚胺 2,3 双加氧酶 (IDO) 负责将色氨酸转化为犬尿氨酸，该途径的失调与焦虑和抑郁等精神疾病有关。本研究评估了乙醇戒断对大鼠的早期和晚期行为和生化影响。在 21 天期间，雄性 Wistar 大鼠在饮用水中接受浓度增加的乙醇。在实验 1 中，对照组和戒断组在去除乙醇后 3、5、10、19 和 21 天接受一系列行为测试。在实验 2 中，动物在停药后 3 天（短期）或 21 天（长期）被安乐死，在对前额叶皮层、海马体和纹状体中的犬尿氨酸浓度进行分析后，将大脑完全解剖。短期乙醇戒断减少了对高架十字迷宫中张开臂的探索。在强迫游泳试验中，长期戒酒的大鼠表现出比对照动物更长的不动时间。乙醇戒断不会改变大鼠的运动和运动协调性。在实验 2 中，长期停药后，前额叶皮层的犬尿氨酸浓度增加。总之，短期乙醇戒断产生焦虑样行为，而长期戒断则有利于抑郁样行为。长期戒酒会提高犬尿氨酸水平，特别是在前额叶皮层，