Wingard Jeffrey C, Packard Mark G
Department of Psychology, Yale University, United States.
Behav Brain Res. 2008 Nov 3;193(1):126-31. doi: 10.1016/j.bbr.2008.05.002. Epub 2008 May 8.
The basolateral amygdala (BLA) is implicated in the neurobiology of emotion, and can also modulate the cognitive and habit memory processes mediated by the hippocampus and dorsal striatum, respectively. In a dual-solution task that can be acquired using either hippocampus-dependent or dorsal striatal-dependent learning, peripheral or intra-BLA infusion of the anxiogenic alpha(2)-adrenoreceptor antagonist RS 79948 biases rats towards the use of habit learning. In view of evidence that anxiety can promote relapse into habitual and maladaptive human behaviors, understanding the mechanism(s) by which emotional arousal can influence the relative use of multiple memory systems may prove clinically relevant. Therefore, the present experiments examined whether intra-BLA infusions of RS 79948 bias rats towards the use of habit learning directly by enhancing dorsal striatal function, or indirectly by impairing hippocampal function. Adult male Long-Evans rats were trained in one of two single-solution water plus-maze tasks. One version required the use of hippocampus-dependent "place" learning. A second version required the use of dorsal striatal-dependent "response" learning, and hippocampal mnemonic processes have been shown to interfere with acquisition of this task. Post-training intra-BLA infusions of RS 79948 (1.0 microg/0.5 microl) impaired acquisition of place learning. In contrast, intra-BLA infusions of RS 79948 enhanced response learning. Intra-BLA infusion of RS 79948 also produced an anxiogenic behavioral profile in an elevated plus-maze at the same dose (1.0 microg) that differentially influenced place and response learning. The findings suggest that intra-BLA infusion of an anxiogenic drug can influence the use of multiple memory systems by impairing hippocampus-dependent learning, thereby releasing habit memory from competing and/or inhibitory influences of cognitive memory.
基底外侧杏仁核(BLA)与情绪的神经生物学有关,并且还可以分别调节由海马体和背侧纹状体介导的认知和习惯记忆过程。在一个可以通过海马体依赖或背侧纹状体依赖学习来习得的双解决方案任务中,向外周或BLA内注射致焦虑的α(2)-肾上腺素能受体拮抗剂RS 79948会使大鼠倾向于使用习惯学习。鉴于有证据表明焦虑会促使人类复归习惯性和适应不良行为,了解情绪唤醒影响多个记忆系统相对使用的机制可能具有临床意义。因此,本实验研究了向BLA内注射RS 79948是直接通过增强背侧纹状体功能,还是间接通过损害海马体功能,使大鼠倾向于使用习惯学习。成年雄性Long-Evans大鼠接受两种单解决方案水迷宫任务之一的训练。其中一个版本需要使用依赖海马体的“位置”学习。第二个版本需要使用依赖背侧纹状体的“反应”学习,并且海马体记忆过程已被证明会干扰该任务的习得。训练后向BLA内注射RS 79948(1.0微克/0.5微升)会损害位置学习的习得。相比之下,向BLA内注射RS 79948可增强反应学习。以相同剂量(1.0微克)向BLA内注射RS 79948在高架十字迷宫中也产生了致焦虑的行为表现,这对位置学习和反应学习有不同影响。研究结果表明,向BLA内注射一种致焦虑药物可通过损害依赖海马体的学习来影响多个记忆系统的使用,从而使习惯记忆从认知记忆的竞争和/或抑制影响中释放出来。