Synergistic effect of [1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one] and antidepressant drugs in the mouse forced swimming test: Possible involvement of serotonergic pathway
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- 作者：Yusuf Ergü ; n ; Ö ; zlem Fatma Orhan ; Ufuk Gü ; ney Ö ; zer ; Gö ; kç ; e Giş ; i
- 关键词：Imipramine ; Fluoxetine ; Desipramine ; Forced swimming ; [1H-[1 ; 2 ; 4]Oxadiazole[4 ; 3-a]quinoxalin-1-one]
- 刊名：European Journal of Pharmacology
- 出版年：2010
- 出版时间：25 March 2010
- 年：2010
- 卷：630
- 期：1-3
- 页码：74-78
- 全文大小：353 K
文摘
To augment the effects of classical antidepressant drugs by combination therapies in drug-resistant patients has been an emerging treatment strategy. In the present study, the potential synergistic effect of [1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one] (ODQ) and antidepressant drugs in the forced swimming test was evaluated. While 5 mg/kg intraperitoneal administration of imipramine, fluoxetine or desipramine caused no effect in the duration of immobility in the forced swimming test (sub-effective doses), higher doses (20, 10 and 10 mg/kg, respectively) reduced the immobility period (effective doses). When sub-effective doses of ODQ (15 mg/kg) and imipramine (5 mg/kg) were applied, there was a significant reduction in the immobility time compared with those of each drug alone. Similarly the reduction seen with the effective dose of imipramine (20 mg/kg) was also augmented by the co-administration of ODQ (15 mg/kg). By its sub-effective dose, ODQ exerted statistically significant augmentations in the responses to either sub-effective (5 mg/kg) or effective dose (10 mg/kg) of fluoxetine. By contrast, desipramine was not influenced by the co-administration of ODQ (15 mg/kg). None of the drugs used in the present study had any effects on the locomotor activity test over the dose range applied. The results show that co-administration of imipramine/fluoxetine and ODQ exhibits a supra-additive effect and that serotonergic rather than noradrenergic pathway may be involved in the synergistic effect of ODQ.