Effects of an α5GABAA inverse agonist on MK-801-induced learning deficits in an incremental repeated acquisition task.
Effects of an α5GABAA inverse agonist on MK-801-induced learning deficits in an incremental repeated acquisition task.
复制标题
α5GABAA 反向激动剂对增量重复采集任务中 MK-801 诱导的学习缺陷的影响。
DOI：
10.1097/fbp.0000000000000053
复制
发表时间：
2014
影响因子：
1.6
通讯作者：
Reed,MirandaN
中科院分区：
文献类型：
--
作者：
Povroznik,JessicaM;Rudy,CarolynC;Hunsberger,HollyC;Tosto,DavidE;Reed,MirandaN
N-甲基-D-天冬氨酸受体（NMDARs）是多种突触可塑性所必需的，在学习和记忆中起着关键作用。NMDAR功能的缺陷可能是与衰老和许多疾病相关的学习和记忆缺陷的部分原因。MK-801（一种非竞争性NMDAR拮抗剂）的给药通常用作NMDAR功能障碍的临床前模型。本研究的目的是评估α 5 GABA A受体抑制对MK-801急性给药诱导的增量重复获得（IRA）任务中学习缺陷的影响。IRA任务通常用于检查影响学习的因素，从一个单一的反应开始，随着行为符合预设标准，在整个单一会话中逐渐增加到更长的链。MK-801（0.03 - 0.5 mg/kg，腹膜内）在试验前10分钟给药，在剂量大于或等于0.25 mg/kg时，IRA性能指标出现显著剂量依赖性降低。用α 5 GABA A受体反向激动剂L-655，708（1 mg/kg，腹腔内）处理后，MK-801诱导的缺陷减弱。本研究为进一步深入的确定性研究提供了关注点，并支持了进一步深入的确定性研究的可行性，这些研究将α 5 GABA A受体抑制作为减轻NMDAR相关缺陷的合适候选药物。
N-methyl-D-aspartate receptors (NMDARs) are essential for several kinds of synaptic plasticity and play a critical role in learning and memory. Deficits in NMDAR functioning may be partially responsible for the learning and memory deficits associated with aging and numerous diseases. Administration of MK-801, a noncompetitive NMDAR antagonist, is commonly used as a preclinical model of NMDAR dysfunction. The objective of this study was to assess the effects of α 5 GABA A receptor inhibition on learning deficits in the incremental repeated acquisition (IRA) task induced by acute MK-801 administration. The IRA task, commonly used to examine factors that affect learning, begins with a single response and increments to progressively longer chains throughout a single session as behavior meets preset criteria. MK-801 (0.03–0.5 mg/kg, intraperitoneally), administered 10 min pretesting, produced a significant dose-dependent decrease in measures of IRA performance at doses greater than or equal to 0.25 mg/kg. The MK-801-induced deficit was attenuated after treatment with an α 5 GABA A receptor inverse agonist, L-655,708 (1 mg/kg, intraperitoneally). The present study provides the focus for, and supports the feasibility of, further in-depth definitive studies examining α 5 GABA A receptor inhibition as a suitable candidate for the attenuation of NMDAR-related deficits.