Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Neurobiol Learn Mem. 2010 Jul;94(1):83-90. doi: 10.1016/j.nlm.2010.04.004. Epub 2010 Apr 18.
Interaction of cholinergic and glutamatergic inputs in the ventral tegmental area (VTA) influencing a learned behavior is a topic of great interest. In the present study the effect of intra-VTA administration of a nonselective muscarinic acetylcholine antagonist, scopolamine, and N-methyl-d-aspartate (NMDA) receptor agents by themselves as well as their interactions on consolidation and retrieval of inhibitory avoidance (IA) memory have been investigated. A step-through inhibitory avoidance task was used for memory assessment in male Wistar rats. The results showed that intra-VTA administration of scopolamine (1 and 2microg/rat) and NMDA receptor antagonist, MK-801 (0.75 and 1microg/rat) immediately after training, impaired consolidation of IA memory. Interestingly, co-administration of an ineffective dose of MK-801 (0.5microg/rat) with ineffective doses of scopolamine (0.25 and 0.5microg/rat) significantly decreased the consolidation process. Post-training intra-VTA injections of NMDA (0.001 and 0.01microg/rat) had no effects by itself, whereas its co-administration with scopolamine (2microg/rat) prevented the effect of the later drug. The results also showed that pre-test intra-VTA administration of scopolamine (3 and 4microg/rat) and MK-801 (1 and 2microg/rat) impaired retrieval of the IA memory. Moreover, co-administration of an ineffective dose of MK-801 (0.5microg/rat) with ineffective doses of scopolamine (1 and 2microg/rat) increasingly reduced the retrieval of the IA memory. On the contrary to its post-training treatment, pre-test administration of NMDA either alone or in combination with scopolamine caused no significant effect on retrieval of IA memory. It can be concluded that muscarinic acetylcholine and NMDA glutamate receptors in the VTA are involved in the mechanism(s) underlying consolidation and retrieval of the IA memory.
腹侧被盖区（VTA）中胆碱能和谷氨酸能输入的相互作用影响习得行为，这是一个非常感兴趣的话题。在本研究中，研究了 VTA 内给予非选择性毒蕈碱乙酰胆碱拮抗剂东莨菪碱和 N-甲基-D-天冬氨酸（NMDA）受体激动剂本身及其相互作用对抑制性回避（IA）记忆的巩固和检索的影响。使用一步式抑制性回避任务评估雄性 Wistar 大鼠的记忆。结果表明，训练后立即 VTA 内给予东莨菪碱（1 和 2μg/大鼠）和 NMDA 受体拮抗剂 MK-801（0.75 和 1μg/大鼠）可损害 IA 记忆的巩固。有趣的是，给予无效剂量的 MK-801（0.5μg/大鼠）与无效剂量的东莨菪碱（0.25 和 0.5μg/大鼠）共同给药显著降低了巩固过程。NMDA（0.001 和 0.01μg/大鼠）在训练后 VTA 内注射本身没有影响，而与东莨菪碱（2μg/大鼠）共同给药可防止后者药物的作用。结果还表明，IA 记忆测试前 VTA 内给予东莨菪碱（3 和 4μg/大鼠）和 MK-801（1 和 2μg/大鼠）可损害 IA 记忆的检索。此外，给予无效剂量的 MK-801（0.5μg/大鼠）与无效剂量的东莨菪碱（1 和 2μg/大鼠）共同给药可逐渐减少 IA 记忆的检索。与训练后治疗相反，NMDA 单独或与东莨菪碱联合给药对 IA 记忆的检索没有显著影响。可以得出结论，VTA 中的毒蕈碱乙酰胆碱和 NMDA 谷氨酸受体参与了 IA 记忆的巩固和检索机制。
