School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, 516 Jun Gong Road, Shanghai, 200093, China.
J Neural Transm (Vienna). 2013 Aug;120(8):1191-9. doi: 10.1007/s00702-013-0973-5. Epub 2013 Jan 12.
Intracerebroventricular (ICV) administration of ouabain, a specific Na-K-ATPase inhibitor, in rats mimics the manic phenotypes of bipolar disorder and thus has been proposed as one of the best animal models of mania. Bipolar mania has been known to be associated with dysfunctions of medial prefrontal cortex (mPFC), a brain area critically involved in mental functions; however, the exact mechanism underlying these dysfunctions is not yet clear. The present study investigated synaptic transmission, synaptic plasticity, and dopamine release in Sprague-Dawley rat mPFC following ICV administration of ouabain (5 μl of 1 mM ouabain). The electrophysiological results demonstrated that ouabain depressed the short- and the long-term synaptic plasticity, represented by paired-pulse facilitation and long-term potentiation, respectively, in the mPFC. These ouabain-induced alterations in synaptic plasticity can be prevented by pre-treatment with lithium (intraperitoneal injection of 47.5 mg/kg lithium, twice a day, 7 days), which acts as an effective mood stabilizer in preventing mania. The electrochemical results demonstrated that ICV administration of ouabain enhanced dopamine release in the mPFC, which did not be affected by pre-treatment with lithium. These findings suggested that alterations in synaptic plasticity and dopamine release in the mPFC might underlie the dysfunctions of mPFC accompanied with ouabain administration-induced bipolar mania.
脑室（ICV）内给予哇巴因，一种特定的 Na-K-ATP 酶抑制剂，可模拟双相情感障碍的躁狂表型，因此被认为是躁狂的最佳动物模型之一。已知双相情感障碍的躁狂与内侧前额叶皮层（mPFC）的功能障碍有关，mPFC 是一个与精神功能密切相关的大脑区域；然而，这些功能障碍的确切机制尚不清楚。本研究在 Sprague-Dawley 大鼠 mPFC 中，通过脑室内给予哇巴因（5μl 1mM 哇巴因），研究了突触传递、突触可塑性和多巴胺释放。电生理结果表明，哇巴因抑制了 mPFC 中的短时间和长时程突触可塑性，分别表现为成对脉冲易化和长时程增强。这些哇巴因诱导的突触可塑性改变可以通过锂预处理（腹腔内注射 47.5mg/kg 锂，每天两次，7 天）来预防，锂作为一种有效的情绪稳定剂，可预防躁狂。电化学结果表明，脑室内给予哇巴因增强了 mPFC 中的多巴胺释放，而锂预处理对此没有影响。这些发现表明，mPFC 中的突触可塑性和多巴胺释放改变可能是脑室内哇巴因给药诱导的双相情感障碍伴发 mPFC 功能障碍的基础。
