Effect of lithium on behavioral disinhibition induced by electrolytic lesion of the median raphe nucleus.
Effect of lithium on behavioral disinhibition induced by electrolytic lesion of the median raphe nucleus.
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DOI：
10.1007/s00213-014-3775-z
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发表时间：
2015-04
影响因子：
3.4
通讯作者：
Gould, Todd D.
中科院分区：
文献类型：
--
作者：
Pezzato, Fernanda A.;Can, Adem;Hoshino, Katsumasa;Horta, Jose de Anchieta C., Jr.;Mijares, Miriam G.;Gould, Todd D.
脑干回路的改变被认为是情绪障碍病因学的一个可能机制。中缝正中核（MnR）的投射调节前脑中的多巴胺能活性，也是行为去抑制/抑制系统的一部分，该系统产生类似于双相情感障碍躁狂和抑郁阶段表现出的行为变化的表型。评估慢性锂治疗对MnR损伤诱导的行为去抑制的影响。对C57 BL/6 J小鼠进行MnR电解损伤，假手术组和正常对照组作为对照。恢复后，用锂（LiCl，添加在食物中）长期处理小鼠，然后进行行为测试。MnR损伤引起躁狂样行为改变，包括开放视野（OF）中的多动、刻板的绕圈、高架十字迷宫（ESTA）和光/暗盒（LDB）测试中的抗焦虑/冒险以及基础体温升高。锂在减少OF多动和刻板方面特别有效，但对焦虑/冒险措施没有逆转（ESTA）或非特异性影响（LDB）。此外，锂降低了糖精偏好，并防止在单次饲养期间体重减轻。我们的数据支持电解质损伤的MnR作为一个实验模型的一个超兴奋/去抑制表型符合躁狂症的某些方面，由情绪稳定剂锂衰减。考虑到锂在治疗躁狂症方面的相对特异性功效，这些数据支持这样的假设，即躁狂症状不仅来自兴奋系统的刺激，而且来自抑制机制的失活或活性降低。
Alterations in brainstem circuits have been proposed as a possible mechanism underlying the etiology of mood disorders. Projections from the median raphe nucleus (MnR) modulate dopaminergic activity in the forebrain and are also part of a behavioral disinhibition/inhibition system that produces phenotypes resembling behavioral variations manifested during manic and depressive phases of bipolar disorder. Assess the effect of chronic lithium treatment on behavioral disinhibition induced by MnR lesions. MnR electrolytic lesions were performed in C57BL/6J mice, with sham operated and intact animals as control groups. Following recovery, mice were chronically treated with lithium (LiCl, added in chow) followed by behavioral testing. MnR lesion induced manic-like behavioral alterations including hyperactivity in the open field (OF), stereotyped circling, anxiolytic/risk taking in the elevated plus maze (EPM) and light/dark box (LDB) tests, and increased basal body temperature. Lithium was specifically effective in reducing OF hyperactivity and stereotypy but did not reverse (EPM) or had a nonspecific effect (LDB) on anxiety/risk taking measures. Additionally, lithium decreased saccharin preference and prevented weight loss during single housing. Our data support electrolytic lesions of the MnR as an experimental model of a hyper-excitable/disinhibited phenotype consistent with some aspects of mania that are attenuated by the mood stabilizer lithium. Given lithium’s relatively specific efficacy in treating mania, these data support the hypothesis that manic symptoms derive not only from the stimulation of excitatory systems but also from inactivation or decreased activity of inhibitory mechanisms.
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