Lateral hypothalamic kindling induces manic-like behavior in rats: a novel animal model.
Lateral hypothalamic kindling induces manic-like behavior in rats: a novel animal model.
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DOI：
10.1186/s40345-014-0007-8
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发表时间：
2014-12
影响因子：
4
通讯作者：
Choi DS
中科院分区：
文献类型：
--
作者：
Abulseoud OA;Camsari UM;Ruby CL;Mohamed K;Abdel Gawad NM;Kasasbeh A;Yüksel MY;Choi DS
外侧下丘脑整合了关键的生理功能，如睡眠-觉醒周期、能量消耗和性行为。在躁狂症期间，这些功能严重失调。在本研究中，我们通过双侧下丘脑外侧区点燃(LHK)成功地诱导了成年雄性Wistar大鼠的躁狂样行为表型。为了验证模型的有效性，我们研究了标准抗躁狂药物锂(47.5 mg/kg)或丙戊酸(200 mg/kg)每日两次连续15天对LHK大鼠躁狂样行为的影响。与点燃前相比，LHK大鼠在点燃期间表现出明显的性自我刺激(P = 0.034)、过度饲养(P = 0.0005)、摄食(P = 0.013)和梳理(P = 0.007)。与基础酒精摄入量相比，LHK大鼠在躁狂诱导期间也喝了更多的酒精(P = 0.01)。此外，与基线活动水平和休息间隔相比，LHK大鼠在躁狂诱导期和躁狂期后表现出总的运动活动增加(P = 0.001)，而休息间隔减少(P <； 0.02)。长期服用锂或丙戊酸可显著减轻LHK模型大鼠的躁狂样行为。鉴于LHK大鼠的行为表型和对标准抗躁狂药物的反应，LHK大鼠可能为研究人类躁狂精神病理学提供一个模型。本文的在线版本(doi：10.1186/s40345-0140007-8)包含补充材料，授权用户可以使用。
The lateral hypothalamus integrates critical physiological functions such as the sleep-wake cycle, energy expenditure, and sexual behaviors. These functions are severely dysregulated during mania. In this study, we successfully induced manic-like behavioral phenotypes in adult, male Wistar rats through bilateral lateral hypothalamic area kindling (LHK). To test the validity of the model, we studied the effect of standard antimanic medications lithium (47.5 mg/kg) or valproic acid (200 mg/kg) twice/day for 15 days in attenuating manic-like behaviors in the LHK rat. Compared with pre-kindling behaviors, LHK rats displayed significantly increased sexual self-stimulation (P = 0.034), excessive rearing (P = 0.0005), feeding (P = 0.013), and grooming (P = 0.007) during the kindling interval. LHK rats also drank more alcohol during the mania-induction days compared with baseline ethanol consumption levels (P = 0.01). Moreover, LHK rat exhibited increased total locomotor activity (P = 0.02) with reduced rest interval (P < 0.001) during the mania induction and post-mania days compared with baseline activity levels and rest intervals. Chronic administration of lithium or valproic acid significantly attenuated manic-like behaviors in the LHK rat model. Given the behavioral phenotype and the response to standard antimanic medications, the LHK rats may provide a model for studying manic psychopathology in humans. The online version of this article (doi:10.1186/s40345-014-0007-8) contains supplementary material, which is available to authorized users.