期刊
HORMONES AND BEHAVIOR
卷 64, 期 1, 页码 1-7出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.yhbeh.2013.04.009
关键词
Melatonin; Neu-P11; Memory; Alzheimer' disease; Rats
资金
- National Natural Science Foundation of China [81171281]
- Neurim Pharmaceuticals Research Grant
- Hunan Provincial Natural Science Foundation of China [10JJ2009]
- Science and Technology Development Project of Hengyang Municipal Science and Technology Bureau [2012KJ37]
Previous studies have shown that melatonin is implicated in modulating learning and memory processing. Melatonin also exerts neuroprotective activities against A beta-induced injury in vitro and in vivo. Neu-P11 (piromelatine, N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-4-oxo-4H-pyran-2-carboxamide) is a novel melatonin (MT1/MT2) receptor agonist and a serotonin 5-HT1A/1D receptor agonist recently developed for the treatment of insomnia. In the present study we firstly investigated whether Neu-P11 and melatonin enhance memory performance in the novel object recognition (NOR) task in rats, and then assessed whether Neu-P11 and melatonin improve neuronal and cognitive impairment in a rat model of Alzheimer' disease (AD) induced by intrahippocampal A beta((1-42)) injection. The results showed that a single morning or afternoon administration of Neu-P11 enhanced object recognition memory measured at 4 or 24 h after training. Melatonin was effective in the memory facilitating effects only when administered in the afternoon. Further results showed that intrahippocampal A beta((1-42)) injection resulted in hippocampal cellular loss, as well as decreased learning ability and memory in the Y maze and NOR tasks in rats. Neu-P11 but not melatonin attenuated cellular loss and cognitive impairment in the rat AD model. The current data suggest that Neu-P11 may serve as a novel agent for the treatment of AD. (C) 2013 Elsevier Inc. All rights reserved.
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