Analysis of the role of the 5-HT1B receptor in spatial and aversive learning in the rat
Analysis of the role of the 5-HT1B receptor in spatial and aversive learning in the rat
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DOI：
10.1038/sj.npp.1300235
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发表时间：
2003-09-01
影响因子：
7.6
通讯作者：
Ögren, SO
中科院分区：
文献类型：
--
作者：
Åhlander-Lüttgen, M;Madjid, N;Ögren, SO
本研究探讨了5-HT1B受体在学习和记忆中的作用。观察了5-HT1B受体激动剂安替托林和选择性5-HT1B受体拮抗剂NAS-181对大鼠在水迷宫(WM)中的空间学习和在被动回避(PA)任务中的厌恶学习的影响。安非托林(0.1-1.0 mg/kg，S.C.)在WM和PA任务中均引起学习和记忆的剂量依赖性损害。NAS-181(1.0-10 mg/kg，S.C.)未能改变WM任务的性能，但产生了剂量依赖的(0.1-20 mg/kg)促进PA保留。此外，NAS-181(10 mg/kg)可完全阻断安非他林(1.0 mg/kg)对WM和PA的影响。而NAS-181(3.0~10 mg/kg)不能改善非选择性M受体拮抗剂东莨菪碱(WM任务0.1 mg/kg，PA任务0.3 mg/kg，S.C.)所致的空间学习障碍和PA保持障碍。阈值以下剂量(0.1 mg/kg)可阻断NAS-181(1.0-10 mg/kg)诱导的PA滞留。此外，在工作记忆任务中，分析了由安非他林和东莨菪碱引起的行为障碍(如运动障碍和平台偏斜)，并与工作记忆成绩进行了相关分析。这些结果表明：(1)刺激和阻断5-HT1B受体在大鼠两种类型的认知任务中产生相反的作用；(2)5-HT1B拮抗剂NAS-181可促进认知功能的某些方面，很可能是通过增加胆碱能传递。这些结果表明，5-HT1B受体拮抗剂可能在治疗胆碱能传递障碍所致的认知障碍方面具有潜力。
The present study examined the role of the 5-HT1B receptor in learning and memory. The ability of the 5-HT1B receptor agonist anpirtoline and the selective 5-HT1B receptor antagonist NAS-181 to affect spatial learning in the water maze (WM) and aversive learning in the passive avoidance (PA) task were examined in the rat. Anpirtoline (0.1-1.0 mg/kg, s.c.) caused a dose-dependent impairment of learning and memory in both the WM and PA tasks. NAS-181 (1.0-10 mg/kg, s.c.) failed to alter performance of the WM task, but produced a dose-dependent (0.1-20 mg/kg) facilitation of PA retention. Furthermore, treatment with NAS-181(10 mg/kg) fully blocked the impairment of the WM and PA performance caused by anpirtoline (1.0 mg/kg). In contrast, NAS-181 (3.0-10 mg/kg) did not attenuate the spatial learning deficit and the impairment of PA retention caused by scopolamine (0.1 mg/kg in WM task, 0.3 mg/kg in PA task, s.c.), a nonselective muscarinic antagonist. Moreover, a subthreshold dose of scopolamine (0.1 mg/kg) blocked the facilitation of PA retention induced by NAS-181 (1.0-10 mg/kg). In addition, the behavioral disturbances (eg thigmotaxic swimming and platform deflections) induced by anpirtoline and scopolamine were analyzed in the WM task and correlated with WM performance. These results indicate that: (1) 5-HT1B receptor stimulation and blockade result in opposite effects in two types of cognitive tasks in the rat, and that (2) the 5-HT1B antagonist NAS-181 can facilitate some aspects of cognitive function, most likely via an increase of cholinergic transmission. These results suggest that 5-HT1B receptor antagonists may have a potential in the treatment of cognitive deficits resulting from loss of cholinergic transmission.