Bertotto M E, Bustos S G, Molina V A, Martijena I D
Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria 5000, Córdoba, Argentina.
Neuroscience. 2006 Nov 3;142(4):979-90. doi: 10.1016/j.neuroscience.2006.07.013. Epub 2006 Aug 23.
Animals made dependent via an ethanol (ETOH) -containing liquid diet (6% v/v) for 14 days were subjected to a contextual fear conditioning paradigm 3 days after the last consumption day. After conditioning, rats were subjected to four extinction trials by exposing the animals to the conditioned context and their freezing was evaluated for each trial. Immediately after the first extinction trial, animals were injected with D-cycloserine (DCS) 5 mg/kg i.p., a dose that did not influence the extinction in control rats. Spontaneous recovery of learned fear was tested seven days after the last extinction trial. The following day, animals were subjected to a reacquisition or a reinstatement procedure and their freezing responses evaluated 24 h later. The present study shows that: 1. discontinuation from chronic ETOH administration facilitated the formation of a new fear memory concomitant with a marked resistance to being extinguished, 2. administration of DCS (5 mg/kg) facilitated the extinction process only in ETOH withdrawn rats, 3. both reinstatement and reacquisition procedures restored the increased freezing in ETOH withdrawn animals after extinction, 4. DCS administered immediately after the first extinction trial prevented the increase in freezing following both reacquisition and reinstatement. The enhanced sensitivity to the facilitatory effect of DCS in ETOH withdrawn animals may be mediated by adaptive changes in N-methyl-D-aspartate (NMDA) receptor provoked by ETOH dependence.
通过含乙醇（ETOH）的液体饲料（6% v/v）使其产生依赖14天的动物，在最后一次摄入日3天后接受情境恐惧条件反射范式实验。条件反射训练后，通过将大鼠置于条件化情境中对其进行四次消退试验，并对每次试验中的僵立反应进行评估。在第一次消退试验后立即给动物腹腔注射5 mg/kg的D -环丝氨酸（DCS），该剂量对对照大鼠的消退反应没有影响。在最后一次消退试验7天后测试习得性恐惧的自发恢复情况。第二天，对动物进行重新习得或恢复程序，并在24小时后评估其僵立反应。本研究表明：1. 停止长期给予ETOH促进了新恐惧记忆的形成，同时伴有对消退的显著抗性；2. 给予DCS（5 mg/kg）仅在戒断ETOH的大鼠中促进了消退过程；3. 恢复程序和重新习得程序均使戒断ETOH的动物在消退后僵立反应增加；4. 在第一次消退试验后立即给予DCS可防止重新习得和恢复后僵立反应的增加。戒断ETOH的动物对DCS促进作用的敏感性增强可能是由ETOH依赖引发的N -甲基 - D -天冬氨酸（NMDA）受体的适应性变化介导的。
