Andrzejewski M E, Spencer R C, Kelley A E
Department of Psychiatry, University of Wisconsin-Madison, Madison, WI 53719, USA.
Neuroscience. 2005;135(2):335-45. doi: 10.1016/j.neuroscience.2005.06.038.
Substantial experimental evidence exists suggesting a critical role for dopamine in reinforcer-related processes, such as learning and drug addiction. Dopamine receptors, and in particular D1 receptors, are widely considered as modulators of synaptic plasticity. The amygdala contains both dopamine terminals and dopamine D1 receptors and is intimately involved in motivation and learning. However, little is known about the involvement of D1 receptor activation in two subnuclei of the mammalian amygdala, the central nucleus and basolateral complex in instrumental learning. Following recovery from surgery and preliminary training, rats with bilateral indwelling cannulae aimed at the central nucleus or basolateral complex were trained to lever-press for sucrose pellets over 12 sessions. Infusion of the selective D1 antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (0.3 nmol and 3.0 nmol) prior to the first five training sessions dose-dependently impaired instrumental learning when compared with vehicle-infused controls. All rats were then exposed to five sessions drug-free; lever-pressing quickly reached equal levels across groups. A drug infusion prior to an 11th session revealed no effect on performance. Control experiments indicated that basic motivational processes and general motor responses were intact, such as spontaneous feeding and locomotor activity. These results show an essential role for D1-receptor activation in both the central nucleus and basolateral complex on the acquisition of lever pressing for sucrose pellets in rats, but not the performance of the behavior once conditioned. We propose that instrumental learning is dependent on plasticity in the central nucleus and basolateral complex amygdala, and that D1 receptor activation participates in transcriptional processes that underlie this plasticity.
大量实验证据表明多巴胺在强化物相关过程中发挥关键作用,如学习和药物成瘾。多巴胺受体,尤其是D1受体,被广泛认为是突触可塑性的调节因子。杏仁核既含有多巴胺终末,也含有多巴胺D1受体,并且与动机和学习密切相关。然而,关于D1受体激活在哺乳动物杏仁核的两个亚核——中央核和基底外侧复合体在工具性学习中的作用,人们所知甚少。在从手术中恢复并经过初步训练后,将双侧留置套管对准中央核或基底外侧复合体的大鼠在12节训练课程中接受训练,通过按压杠杆获取蔗糖颗粒。在最初的五节训练课程之前注入选择性D1拮抗剂盐酸R(+)-7-氯-8-羟基-3-甲基-1-苯基-2,3,4,5-四氢-1H-3-苯并氮杂䓬(0.3纳摩尔和3.0纳摩尔),与注入赋形剂的对照组相比,剂量依赖性地损害了工具性学习。然后所有大鼠接受五节无药物课程;各组的杠杆按压行为迅速达到相同水平。在第11节课程之前注入药物对行为表现没有影响。对照实验表明基本的动机过程和一般运动反应是完整的,如自发进食和运动活动。这些结果表明,D1受体激活在大鼠获取蔗糖颗粒的杠杆按压行为的习得过程中,对中央核和基底外侧复合体都起着至关重要的作用,但对该行为一旦形成后的表现则没有影响。我们提出,工具性学习依赖于杏仁核中央核和基底外侧复合体的可塑性,并且D1受体激活参与了构成这种可塑性基础的转录过程。