Walz Julio C, Frey Benício N, Andreazza Ana C, Ceresér Keila M, Cacilhas Alice A, Valvassori Samira S, Quevedo João, Kapczinski Flávio
Bipolar Disorders Program, Centro de Pesquisas, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos, 2350, 90035-003 Porto Alegre, RS, Brazil.
J Psychiatr Res. 2008 Apr;42(5):416-21. doi: 10.1016/j.jpsychires.2007.03.005. Epub 2007 May 21.
It has been demonstrated that lithium (Li) and valproate (VPT), first line mood stabilizers, increase BDNF content in rat hippocampus and frontal cortex, which suggests that the regulation of neurotrophic factors might be associated with their pharmacological effects. In sight of the scarcity of studies with other neurotrophins, and the possible relevance of multiple neurotrophic signaling systems in bipolar disorder we investigated the effects of Li and VPT on NT-3 levels in rat serum and hippocampus, using an animal model of mania induced by amphetamine (AMPH). In the reversal model, adult male Wistar rats received AMPH or saline for 14 days, and between the 8th and 14th days, animals were treated with Li, VPT or saline. In the prevention model, rats were pretreated with Li, VPT or saline, and between the 8th and 14th days, the animals received AMPH or saline. Li increased serum and hippocampal NT-3 levels in all conditions, whereas VPT increased hippocampal NT-3 in the prevention model only. Li reversed AMPH changes in NT-3 in the reversal model, and VPT prevented AMPH changes in NT-3 in the prevention model. These results suggest that both Li and VPT modulate serum and central (hippocampal) NT-3 levels, and further support that the regulation of neurotrophic signaling systems may be related to the mechanisms of action of mood stabilizers.
已有研究表明，一线心境稳定剂锂盐（Li）和丙戊酸盐（VPT）可增加大鼠海马体和前额叶皮质中的脑源性神经营养因子（BDNF）含量，这表明神经营养因子的调节可能与其药理作用相关。鉴于针对其他神经营养因子的研究较少，且双相情感障碍中多种神经营养信号系统可能具有相关性，我们使用苯丙胺（AMPH）诱导的躁狂动物模型，研究了Li和VPT对大鼠血清和海马体中神经营养因子-3（NT-3）水平的影响。在逆转模型中，成年雄性Wistar大鼠接受AMPH或生理盐水处理14天，在第8天至第14天期间，动物接受Li、VPT或生理盐水治疗。在预防模型中，大鼠预先接受Li、VPT或生理盐水处理，在第8天至第14天期间，动物接受AMPH或生理盐水。Li在所有条件下均增加血清和海马体中的NT-3水平，而VPT仅在预防模型中增加海马体中的NT-3水平。Li在逆转模型中逆转了AMPH引起的NT-3变化，VPT在预防模型中预防了AMPH引起的NT-3变化。这些结果表明，Li和VPT均可调节血清和中枢（海马体）NT-3水平，并进一步支持神经营养信号系统的调节可能与心境稳定剂的作用机制有关。
