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首页> 外文期刊>Kaohsiung Journal of Medical Sciences >Effects of agomelatine in a murine model of obsessive–compulsive disorder: Interaction with meta-chlorophenylpiperazine, bicuculline, and diazepam
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Effects of agomelatine in a murine model of obsessive–compulsive disorder: Interaction with meta-chlorophenylpiperazine, bicuculline, and diazepam

机译：阿戈美拉汀在强迫症小鼠模型中的作用：与 meta -氯苯基哌嗪，双瓜氨酸和地西epa的相互作用

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The anticompulsive potential of agomelatine, a potent MT 1/2 receptor agonist, and its combined effect with m -chlorophenylpiperazine hydrochloride (mCPP), bicuculline, and diazepam, were investigated in male C57BLJ/6 mice using marble-burying behavior (MBB) test. Acute administration of agomelatine (30–40?mg/kg, intraperitoneal (i.p.)) significantly inhibited the MBB in mice without influencing their locomotor activity. Further, chronic (28 days) administration of lower doses of agomelatine (10 and 20?mg/kg, i.p.) dose-dependently reduced the MBB without influencing their locomotor activity. Interaction studies revealed that pretreatment with mCPP (0.5?mg/kg, i.p.), a serotonin 5HT 2C agonist, partially attenuated the anticompulsive effect of agomelatine (30?mg/kg). Further, a GABA A receptor agonist (diazepam, 1.25?mg/kg, i.p.) and antagonist (bicuculline, 1?mg/kg, i.p.) had no influence on the effects of agomelatine on MBB and locomotor activity. The doses of modulators were selected on the basis of dose-response studies. The results indicate that agomelatine has a potent anticompulsive effect that can be attributed to 5HT 2C antagonism and MT 1/2 agonism, and is certainly not mediated via its effects on the GABAergic system. Thus, the study adds to the growing literature on the psychopharmacological effects of agomelatine, and warrants further exploration in multiple paradigms.
机译：在C57BLJ / 6雄性小鼠中，使用大理石掩埋行为（MBB）测试研究了强效MT 1/2受体激动剂阿戈美拉汀的抗强迫潜力及其与盐酸间氯苯哌嗪（mCPP），双小分子和地西epa的联合作用。 。急性施用阿戈美拉汀（30-40 mg / kg，腹膜内（腹腔））可显着抑制小鼠的MBB，而不会影响其运动活性。此外，长期（28天）服用较低剂量的阿戈美拉汀（10和20？mg / kg，腹腔注射）剂量依赖性地降低了MBB，而不影响其运动活性。相互作用研究表明，用5-羟色胺5HT 2C激动剂mCPP（0.5？mg / kg，腹腔注射）进行预处理可部分减弱阿戈美拉汀（30？mg / kg）的抗强迫作用。此外，GABA A受体激动剂（地西p，1.25μmg/ kg，腹膜内）和拮抗剂（比库林，1μmg/ kg，腹膜内）对阿戈美拉汀对MBB和运动活性的影响没有影响。根据剂量反应研究选择调节剂的剂量。结果表明阿戈美拉汀具有有效的抗强迫作用，可归因于5HT 2C拮抗作用和MT 1/2激动作用，并且肯定不是通过其对GABA能系统的作用介导的。因此，这项研究增加了关于阿戈美拉汀的心理药理作用的文献，并且有必要在多种范式中进行进一步的探索。

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