Patti C L, Kameda S R, Carvalho R C, Takatsu-Coleman A L, Lopez G B, Niigaki S T, Abílio V C, Frussa-Filho R, Silva R H
Department of Pharmacology, Universidade Federal de São Paulo, Rua Botucatu, 862-Ed. Leal Prado, 04023-062 São Paulo, Brazil.
Psychopharmacology (Berl). 2006 Jan;184(1):1-12. doi: 10.1007/s00213-005-0238-6. Epub 2005 Dec 10.
The amnesic effects of morphine may be related to its action on nociception, anxiety, or locomotion. This effect is also suggested to be related to state dependency.
The aims of this study were to verify the effects of morphine on mice tested in the plus-maze discriminative avoidance task (DAT) that uses light and noise as aversive stimuli and allows the concomitant evaluation of learning, memory, anxiety, and locomotion and also to verify the possible role of state-dependent learning in the effects of morphine.
The DAT was conducted in a modified elevated plus-maze. In the training, the aversive stimuli were applied when mice entered in one of the enclosed arms, whereas in the test, no stimuli were applied. The main results showed that (1) pretraining morphine (5-20 mg/kg i.p.) induced retrieval deficits (evaluated by the time spent in the aversive arm in the test) but not acquisition deficits (evaluated by the decrease in aversive arm exploration along the training); (2) pretest morphine (5-10 but not 20 mg/kg) counteracted this deficit; (3) morphine induced hypolocomotion (decreased number of entries in the arms), irrespective of memory alterations; and (4) morphine did not alter anxiety-like behavior (evaluated by the time spent in the open arms) during the training.
Morphine given before training induces retrieval deficits in mice tested in the DAT, and these deficits could be related to morphine-induced state-dependent learning. Neither the memory deficit induced by pretraining morphine nor the reversal of this deficit by pretest morphine seems to be related to anxiety levels or locomotor alterations.
吗啡的失忆效应可能与其对伤害感受、焦虑或运动的作用有关。这种效应也被认为与状态依存性有关。
本研究的目的是验证吗啡对在以光和噪音作为厌恶刺激的十字迷宫辨别性回避任务（DAT）中测试的小鼠的影响，该任务允许同时评估学习、记忆、焦虑和运动，并且还要验证状态依存性学习在吗啡效应中可能发挥的作用。
DAT在改良的高架十字迷宫中进行。在训练中，当小鼠进入其中一个封闭臂时施加厌恶刺激，而在测试中不施加刺激。主要结果表明：（1）训练前给予吗啡（腹腔注射5 - 20毫克/千克）会导致记忆提取缺陷（通过测试中在厌恶臂停留的时间来评估），但不会导致习得缺陷（通过训练过程中厌恶臂探索次数的减少来评估）；（2）测试前给予吗啡（5 - 10毫克/千克，但20毫克/千克无效）可抵消这种缺陷；（3）吗啡会导致运动减少（进入臂的次数减少），与记忆改变无关；（4）吗啡在训练过程中不会改变类似焦虑的行为（通过在开放臂停留的时间来评估）。
训练前给予吗啡会导致在DAT中测试的小鼠出现记忆提取缺陷，这些缺陷可能与吗啡诱导的状态依存性学习有关。训练前给予吗啡所诱导的记忆缺陷以及测试前给予吗啡对该缺陷的逆转似乎都与焦虑水平或运动改变无关。
