替扎尼定对Balb/c小鼠抗抑郁和抗惊厥电位的神经行为评价

E. Patrick, S. Otimenyin, B. Bukar, B. Chindo, D. Mallam
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摘要

替扎尼定是一种选择性α2-肾上腺素能受体激动剂,通过肾上腺素能通路刺激中枢神经系统。本研究评价了替扎尼定对小鼠的抗抑郁和抗惊厥作用。目前可用的抗抑郁和癫痫药物的各种局限性以及两种神经系统疾病之间的双向关系需要改进药物治疗干预。125只Balb/c小鼠被分为75只和50只,分别用于抗抑郁和抗惊厥研究。采用强迫游泳(FST)、悬尾(TST)和开放场地(OFT)抗抑郁模型。每个模型25只小鼠分为5组(n=5);1 mL/kg蒸馏水组(阴性对照)、15 mg/kg丙咪嗪组(FST和TST阳性对照)、0.05 mg/kg地西泮组(OFT阳性对照)以及1 mg/kg、2 mg/kg和4 mg/kg替扎尼定组。采用戊四唑(PTZ)和微毒素癫痫模型进行抗惊厥药物筛选,小鼠分别给予2 mg/kg、4 mg/kg和8 mg/kg的替扎尼定。各剂量替扎尼定均能显著降低小鼠FST和TST的静止时间(p≤0.0001)。替扎尼定与0.05 mg/kg地西泮在OFT中的交叉频次无显著增加(p > 0.05)。替扎尼定在PTZ模型中显著延迟肌阵挛发作(p≤0.001),而在微毒素模型中无显著延迟(p 0.05)。这项研究表明,替扎尼定具有抗抑郁活性,但抗惊厥活性很小。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Neurobehavioural Evaluation of Antidepressant and Anticonvulsant Potentials of Tizanidine in Balb/c Mice
Tizanidine is a selective α2-adrenergic receptor agonist that stimulates the central nervous system through the adrenergic pathway. This study evaluated the antidepressant and anticonvulsant activity of tizanidine in mice. The various limitations of currently available anti-depressive and epileptic drugs and the bidirectional relationship between the two neurological disorders warrant improved pharmacotherapy interventions. 125 Balb/c mice were divided into 75 and 50 for antidepressant and anticonvulsant stud-ies, respectively. Forced swim (FST), tail suspension (TST), and open field (OFT) antidepressant models were used. In each model, twenty-five mice were divided into five groups (n=5); 1 mL/kg dis-tilled water group (negative control), 15 mg/kg imipramine (positive control in FST and TST), 0.05 mg/kg diazepam (positive control for OFT) group, and 1 mg/kg, 2 mg/kg, and 4 mg/kg tizanidine groups respectively. Anticonvulsant screening was conducted using pentylenetetrazole (PTZ) and picrotoxin models of seizure in which mice were treated with 2 mg/kg, 4 mg/kg and 8 mg/kg tizanidine. Tizanidine at all the doses significantly reduced the immobility time of the mice in FST (p≤0.0001) and TST (p≤ 0.05). There was no significant increase in line crossing frequency between tizanidine and 0.05 mg/kg diazepam in the OFT (p˃0.05). Tizanidine significantly delayed the onset of myoclonic jerks (p≤0.001) in the PTZ model but not in the picrotoxin model (p˃0.05). This study showed that tizanidine possesses antidepressant-like activity, but little anticonvulsant activity.
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