Yim A J, Moraes C R G, Ferreira T L, Oliveira M G M
Department of Psychobiology, Universidade Federal de São Paulo (UNIFESP), Brazil.
Behav Brain Res. 2006 Jul 15;171(1):162-9. doi: 10.1016/j.bbr.2006.03.031. Epub 2006 May 4.
Conditioned place preference is an animal model used to evaluate the affective properties of natural rewards and drugs of abuse. This animal model is a kind of classical conditioning that depends on learning and memory. The basolateral amygdala (BLA) plays an important role in the consolidation and extinction of memory for this task. However, there is a lack of evidence demonstrating protein synthesis dependent reconsolidation following retrieval in conditioned animals. In other words, is it possible to observe morphine-associated place preference if recall of this preference is disrupted? Accordingly, we investigated this hypothesis by BLA infusion of protein synthesis inhibitor, anisomycin, immediately after retrieval (test) in conditioned place preference paradigm. In the first experiment, the conditioned animals were exposed to the two sides of the apparatus for 15 min in a drug-free state during retrieval. In the second experiment, the animals received an injection of morphine (7.5 mg/kg, i.p.) and immediately after, they were exposed to the two sides of the apparatus for 15 min. Finally in the third experiment, after habituation and training in the conditioned place preference task, the animals received an injection of the unconditioned stimulus (morphine, i.p.; 7.5 mg/kg) followed by confinement for 10 min in the morphine-paired compartment (conditioned stimulus) during memory retrieval. For the three experiments the animals were subsequently exposed in a free-drug state to the two sides of the apparatus for the retest. Our results show that the protein synthesis inhibition in all of these experimental designs had no effect on conditioned place preference memory under conditions that would initiate reconsolidation, suggesting that if reconsolidation of a conditioned place preference task exists it is not mediated by protein synthesis in basolateral amygdala. The effect of anisomycin on consolidation of contextual fear conditioning was also investigated as a positive control to assure that the negative results were not due to methodological problems. Using the same dose of anisomycin (62.5 microg/1 microl) in morphine-associated place preference procedures, we have found that this anisomycin dose blocks the consolidation of contextual fear memory, ruling out the possibility that these negative results can be attributed to methodological problem of some sort.
条件性位置偏爱是一种用于评估自然奖赏和滥用药物情感特性的动物模型。这种动物模型是一种依赖学习和记忆的经典条件反射。基底外侧杏仁核(BLA)在该任务的记忆巩固和消退中起重要作用。然而,缺乏证据表明在条件化动物检索后存在蛋白质合成依赖性再巩固。换句话说,如果这种偏爱的回忆被破坏,是否有可能观察到与吗啡相关的位置偏爱?因此,我们在条件性位置偏爱范式中检索(测试)后立即通过向BLA注入蛋白质合成抑制剂茴香霉素来研究这一假设。在第一个实验中,条件化动物在检索期间处于无药物状态下在装置的两侧暴露15分钟。在第二个实验中,动物接受吗啡注射(7.5mg/kg,腹腔注射),之后立即在装置的两侧暴露15分钟。最后在第三个实验中,在条件性位置偏爱任务中适应和训练后,动物接受非条件刺激(吗啡,腹腔注射;7.5mg/kg)注射,随后在记忆检索期间在与吗啡配对的隔室(条件刺激)中禁闭10分钟。对于这三个实验,随后将动物在无药物状态下暴露于装置的两侧进行重新测试。我们的结果表明,在所有这些实验设计中,蛋白质合成抑制在启动再巩固的条件下对条件性位置偏爱记忆没有影响,这表明如果存在条件性位置偏爱任务的再巩固,它不是由基底外侧杏仁核中的蛋白质合成介导的。还研究了茴香霉素对情境恐惧条件反射巩固的影响作为阳性对照,以确保阴性结果不是由于方法学问题。在与吗啡相关的位置偏爱程序中使用相同剂量的茴香霉素(62.5μg/1μl),我们发现该茴香霉素剂量阻断了情境恐惧记忆的巩固,排除了这些阴性结果可归因于某种方法学问题的可能性。