■木脂酸(XA),一种来自木桃木干果的月桂烯二萜,在小鼠和斑马鱼中具有抗焦虑和抗抑郁样活性。我们旨在评估XA在小鼠强迫游泳试验中与选定的抗抑郁药联合使用时的潜在协同抗抑郁作用。
■木安酸(XA)(10,30,100mgkg-1)的抗抑郁作用,氟西汀(Flx)(3,10,30mgkg-1),舍曲林(Sert)(3,10,30mgkg-1),丙咪嗪(Imi)(10,30,100mgkg-1)和氯胺酮(Ket)(0.1,0.3,1.0mgkg-1),在强迫游泳测试中进行了评估。从各自的对数剂量反应曲线确定实现50%不动时间减少的剂量(ED50)。XA和所选择的抗抑郁药以ED50的固定剂量比组合(1/2:1/2、1/4:1/4、1/8:1/8)共同施用,以鉴定实验ED50(ED50mix)。理论ED50(ED50add),使用等值线图确定所有组合的组合,并与ED50mix进行比较以确定相互作用的性质。在开场测试中评估剂量组合对一般运动活性的影响。
■以下XA组合的相互作用指数(γ),XA/Flx,XA/Sert,XA/Imi和XA/Ket分别为0.42、0.41、0.31和0.34。独立样本t检验表明,在XA的所有组合中,实验ED50(ED50mix)均显着低于理论ED50(ED50add),表明协同抗抑郁作用。然而,XA与氯胺酮的组合在所有剂量组合下均显着降低了一般运动活性。
■木酮酸和氟西汀的联合给药,丙咪嗪,舍曲林和氯胺酮在小鼠中产生协同抗抑郁作用。
UNASSIGNED: Xylopic acid (XA), a kaurene diterpene from the dried fruits of Xylopia aethiopica, has anxiolytic- and antidepressant-like activity in mice and zebrafish. We aimed to assess the potential synergistic antidepressant-like effects of XA when combined with selected antidepressants in the mouse forced-swim test.
UNASSIGNED: The antidepressant-like effect of xylopic acid (XA) (10, 30, 100 mgkg-1), fluoxetine (Flx) (3, 10, 30 mgkg-1), sertraline (Sert) (3, 10, 30 mgkg-1), imipramine (Imi) (10, 30, 100 mgkg-1) and ketamine (Ket) (0.1, 0.3, 1.0 mgkg-1), was evaluated in forced swim test. The dose (ED50) that achieved a 50% reduction in immobility time was determined from the respective log-dose response curves. XA and the selected antidepressants were co-administered in fixed-dose ratio combinations (1/2:1/2, 1/4:1/4, 1/8:1/8) of the ED50 to identify the experimental ED50 (ED50mix). The theoretical ED50(ED50add), of all combinations was determined using isobolograms and compared with the ED50mix to identify the nature of the interaction. The effect of dose combinations on general locomotor activity was assessed in the open-field test.
UNASSIGNED: The interaction index (γ) for the following XA combinations, XA/Flx, XA/Sert, XA/Imi and XA/Ket were 0.42, 0.41, 0.31 and 0.34. An independent sample t-test revealed that the experimental ED50 (ED50mix) was significantly lower than the theoretical ED50 (ED50add) in all combinations of XA, indicative of a synergistic antidepressant-like effect. However, combinations of XA with ketamine significantly reduced general locomotor activity at all dose combinations.
UNASSIGNED: The co-administration of xylopic acid and fluoxetine, imipramine, sertraline and ketamine produces a synergistic antidepressant-like effect in mice.