Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
Experimental Medicine Research Center, Tehran University of Medical Sciences, P.O. Box13145-784, Tehran, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2019 Jul;392(7):833-842. doi: 10.1007/s00210-019-01636-z. Epub 2019 Mar 4.
Acute doses of topiramate (TPM) have been shown to reduce immobility time in the mice forced swimming test (FST) through inhibition of the nitric oxide (NO) pathway. Adenosine triphosphate-sensitive potassium (K) channels are known to have an active role in depression. This study investigates the potential participation of K channels in the antidepressant-like effect of TPM through the stimulatory effects of NO. FST and tail suspension tests (TST) were applied to adult male mice for assessment of the antidepressant-like activity of TPM. Different doses of glibenclamide and cromakalim were also applied in order to investigate the involvement of K channels. Fluoxetine was used as a positive control for evaluation of antidepressant-like effects. In addition, each animal's locomotor activity was evaluated by the open-field test (OFT). TPM (30 mg/kg intraperitoneal (i.p.)) had a significant reductive effect on the immobility behavior similar to fluoxetine (20 mg/kg). Co-administration of sub-effective doses of glibenclamide (1 mg/kg i.p.) and TPM (10 mg/kg i.p.) led to significant synergistic effects in FST and TST. Additionally, the results showed that administration of the sub-effective dose of cromakalim (0.1 and 0.3 mg/kg i.p.) blocked the antidepressant-like effects of TPM (30 mg/kg i.p.) in both tests. These interventions had no impact on the locomotor movement of mice in OFT. This study shows that the antidepressant-like activity of TPM may potentially be mediated by the blocking of the K channels.
急性剂量的托吡酯（TPM）已被证明通过抑制一氧化氮（NO）途径来减少强迫游泳试验（FST）中小鼠的不动时间。三磷酸腺苷敏感的钾（K）通道被认为在抑郁症中具有积极作用。本研究通过 NO 的刺激作用，研究了 K 通道在 TPM 抗抑郁样作用中的潜在参与。FST 和悬尾试验（TST）应用于成年雄性小鼠，以评估 TPM 的抗抑郁样活性。还应用了不同剂量的格列本脲和克罗卡林，以研究 K 通道的参与情况。氟西汀被用作评估抗抑郁样作用的阳性对照。此外，通过旷场试验（OFT）评估每个动物的运动活动。TPM（30mg/kg 腹腔内（i.p.））对不动行为的减少作用与氟西汀（20mg/kg）相似。给予亚有效剂量的格列本脲（1mg/kg i.p.）和 TPM（10mg/kg i.p.）的联合给药在 FST 和 TST 中导致显著的协同作用。此外，结果表明，给予亚有效剂量的克罗卡林（0.1 和 0.3mg/kg i.p.）可阻断 TPM（30mg/kg i.p.）在这两种测试中的抗抑郁样作用。这些干预措施对 OFT 中小鼠的运动活动没有影响。本研究表明，TPM 的抗抑郁样活性可能通过阻断 K 通道来介导。
