Bertaina-Anglade Valérie, la Rochelle Christophe Drieu, Boyer Pierre-Alain, Mocaër Elisabeth
Biotrial, Department of Preclinical Pharmacology, Rennes, France.
Behav Pharmacol. 2006 Dec;17(8):703-13. doi: 10.1097/FBP.0b013e3280116e5c.
To confirm the antidepressant-like activity of agomelatine (S 20098), a melatonin agonist and 5-hydroxytryptamine2C antagonist, already reported in the chronic mild stress and forced swimming tests, the effects of agomelatine were investigated in the learned helplessness test and compared with those of imipramine, melatonin and a selective 5-hydroxytryptamine2C antagonist, SB-242 084. Agomelatine was administered for 5 days either once a day or twice a day, and the effects of pretreatment by a melatonin receptor antagonist, S 22153 (20 mg/kg/day), were studied. A deficit in avoidance learning was observed in helpless control animals. Agomelatine (10 mg/kg/day) administered once a day significantly reduced this deficit with an effect similar to that of imipramine. Effects of agomelatine were abolished by S 22153 pretreatment. Melatonin or SB-242 084 did not reduce the deficit of helpless control animals. These results confirm the antidepressant-like activity of agomelatine and suggest a role of melatonin receptors in its mechanism of action.
为证实褪黑素激动剂及5-羟色胺2C拮抗剂阿戈美拉汀（S 20098）在慢性轻度应激和强迫游泳试验中已报道的抗抑郁样活性，我们在习得性无助试验中研究了阿戈美拉汀的作用，并与丙咪嗪、褪黑素及选择性5-羟色胺2C拮抗剂SB-242 084的作用进行比较。阿戈美拉汀每天给药1次或2次，连续给药5天，并研究了褪黑素受体拮抗剂S 22153（20毫克/千克/天）预处理的效果。在无助对照组动物中观察到回避学习缺陷。每天给药1次的阿戈美拉汀（10毫克/千克/天）显著减少了这一缺陷，其效果与丙咪嗪相似。S 22153预处理消除了阿戈美拉汀的作用。褪黑素或SB-242 084未减少无助对照组动物的缺陷。这些结果证实了阿戈美拉汀的抗抑郁样活性，并提示褪黑素受体在其作用机制中发挥作用。
