Biotrial, Department of Preclinical Pharmacology, 7-9 rue J-L Bertrand, 35000 Rennes, France.
Pharmacol Biochem Behav. 2011 Jun;98(4):511-7. doi: 10.1016/j.pbb.2011.02.015. Epub 2011 Feb 22.
The aim of the present study was to evaluate the effects of agomelatine, an antidepressant with melatonergic agonist and 5-HT(2C) antagonist properties, in the rat novel object recognition (NOR) task, a model of short-term episodic memory. To assess the potential involvement of its chronobiotic activity, single intraperitoneal administration of agomelatine and NOR testing were performed either in the evening or in the morning. In both conditions, using a 24h retention interval, vehicle-treated rats did not discriminate between the novel and the familiar object (recognition index was not different from chance performance) while object memory performance of rats treated with agomelatine either in the evening (10 and 40mg/kg) or in the morning (2.5, 10, and 40mg/kg) was significantly improved. Moreover, the selective 5-HT(2C) antagonist SB 242,084 (0.63, 2.5, and 10mg/kg) and melatonin (2.5, 10, and 40mg/kg) displayed also memory facilitating effects in both administration conditions. Finally, thioperamide used as positive reference compound to validate the experimental conditions, demonstrated a memory facilitating effect. In conclusion, agomelatine was shown to possess memory facilitating effects in the rat NOR task and both melatonergic agonist and 5-HT(2C) antagonist properties could be involved in these effects.
本研究旨在评估抗抑郁药阿戈美拉汀（具有褪黑素能激动剂和 5-HT2C 拮抗剂特性）对大鼠新物体识别（NOR）任务的影响，该任务是一种短期情景记忆模型。为了评估其生物钟活性的潜在作用，在晚上或早上单次腹腔内给予阿戈美拉汀并进行 NOR 测试。在这两种情况下，使用 24 小时的保留间隔，给予载体的大鼠不能区分新物体和熟悉物体（识别指数与随机表现无差异），而在晚上（10 和 40mg/kg）或早上（2.5、10 和 40mg/kg）给予阿戈美拉汀的大鼠的物体记忆表现则显著改善。此外，选择性 5-HT2C 拮抗剂 SB 242,084（0.63、2.5、10 和 10mg/kg）和褪黑素（2.5、10 和 40mg/kg）在两种给药条件下也显示出记忆促进作用。最后，噻哌酰胺作为阳性参考化合物用于验证实验条件，证明了其具有记忆促进作用。总之，阿戈美拉汀在大鼠 NOR 任务中表现出记忆促进作用，其褪黑素能激动剂和 5-HT2C 拮抗剂特性可能参与了这些作用。
