Department of Pharmacology, Graduate School of Science and Engineering, University of Toyama, 3190 Gofuku, Toyama 930-8555, Japan; Molecular Genetic Research, Life Science Research Center, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Behav Brain Res. 2013 Nov 15;257:182-8. doi: 10.1016/j.bbr.2013.09.044. Epub 2013 Sep 27.
Pyrethroids, which are widely used insecticides with low acute toxicity in mammals, affect sodium channels in neurons. In primary culture of rat cortical neurons, the type II pyrethroid deltamethrin (DM) markedly enhances the expression of the mRNA of brain-derived neurotrophic factor (BDNF) and exerts neurotrophic effects. In this study, we investigated the antidepressant-like effect of DM in mice. The effects of DM were assessed using the forced swimming test (FST) and were compared with those of type I pyrethroid permethrin (PM). Intraperitoneal administration of DM (5 and 10mg/kg), but not of PM (10mg/kg), increased the expression of BDNF mRNA in the hippocampus. DM, but not PM, significantly decreased the immobility time in the FST, and did not affect locomotor activity and motor coordination, suggesting that DM has an antidepressant-like effect. This effect of DM was inhibited by intracerebroventricular injection of K252a, which is an inhibitor of the BDNF receptor TrkB, indicating that the antidepressant-like effects of DM are mediated by BDNF/TrkB signaling pathways. Repeated administration of DM, but not of PM, also exerted antidepressant-like effects, which were long lasting. The results of the present study suggest that DM possesses antidepressant-like properties, and may be a possible source for the development of drugs to treat neurodegenerative and psychiatric disorders including depression.
拟除虫菊酯是一种在哺乳动物中具有低急性毒性的广泛使用的杀虫剂，它会影响神经元中的钠离子通道。在原代培养的大鼠皮质神经元中，II 型拟除虫菊酯溴氰菊酯（DM）显著增强脑源性神经营养因子（BDNF）的 mRNA 表达，并发挥神经营养作用。在本研究中，我们研究了 DM 在小鼠中的抗抑郁样作用。通过强迫游泳试验（FST）评估 DM 的作用，并将其与 I 型拟除虫菊酯氯菊酯（PM）进行比较。DM（5 和 10mg/kg）而非 PM（10mg/kg）的腹腔给药增加了海马体中 BDNF mRNA 的表达。DM 而非 PM 显著减少了 FST 中的不动时间，且不影响运动活性和运动协调性，提示 DM 具有抗抑郁样作用。DM 的这种作用被脑室内注射 K252a 抑制，K252a 是 BDNF 受体 TrkB 的抑制剂，表明 DM 的抗抑郁样作用是通过 BDNF/TrkB 信号通路介导的。DM 的重复给药，而非 PM，也产生了持久的抗抑郁样作用。本研究的结果表明，DM 具有抗抑郁样特性，可能是开发治疗包括抑郁症在内的神经退行性和精神疾病药物的潜在来源。
