Abulseoud O A, Gawad N A, Mohamed K, Vadnie C, Camsari U M, Karpyak V, Frye M A, Choi D-S
Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
Transl Psychiatry. 2015 Mar 24;5(3):e534. doi: 10.1038/tp.2015.30.
Sex differences have been observed in mania phenotypes in humans. However the mechanisms underlying this difference are poorly understood. Activating the lateral hypothalamus is implicated in manic-like behaviors in rodents. Using newly established lateral hypothalamus kindled (LHK) rat mania model, we investigated sex differences of manic-like behaviors and its correlation with voluntary ethanol intake. We stimulated the lateral hypothalamus bilaterally in the male and female Wistar rats over five consecutive days. We recorded and quantified kindling-induced behaviors for each individual animal. We also assessed ethanol consumption using a two-bottle choice ethanol drinking as well as circadian locomotor activity counts daily throughout the experiment. We found notable sex differences in several aspects of manic-like behaviors during kindling. Males exhibited a significantly increased locomotor activity during the light phase, and reduced rest interval. On the other hand, females displayed significantly higher ethanol consumption and more frequent rearing behavior. However, no sex differences were present in the duration of sexual, feeding or grooming behaviors or in dark-phase activity counts. The excessive alcohol intake in LHK female rats is reminiscent of clinically reported sex differences in bipolar patients while the other phenotypic sex differences such as rearing and locomotor activity are less clearly described in clinical studies. Overall, our results lend further evidence for the validity of the LHK rat as a useful model to study brain region-specific molecular changes during mania and its correlation with alcohol use disorders.
在人类躁狂症表型中已观察到性别差异。然而，这种差异背后的机制却知之甚少。激活下丘脑外侧与啮齿动物的躁狂样行为有关。我们使用新建立的下丘脑外侧点燃（LHK）大鼠躁狂模型，研究了躁狂样行为的性别差异及其与自愿乙醇摄入量的相关性。我们在雄性和雌性Wistar大鼠双侧刺激下丘脑外侧，持续五天。我们记录并量化了每只动物的点燃诱导行为。在整个实验过程中，我们还使用双瓶选择乙醇饮用以及每日昼夜运动活动计数来评估乙醇消耗量。我们发现在点燃过程中，躁狂样行为的几个方面存在显著的性别差异。雄性在光照阶段的运动活动显著增加，休息间隔缩短。另一方面，雌性表现出显著更高的乙醇消耗量和更频繁的竖毛行为。然而，在性行为、进食或梳理行为的持续时间或暗相活动计数方面不存在性别差异。LHK雌性大鼠的过量酒精摄入让人联想到临床报告的双相情感障碍患者的性别差异，而其他表型性别差异，如竖毛和运动活动，在临床研究中描述得不太清楚。总体而言，我们的结果进一步证明了LHK大鼠作为研究躁狂期间脑区特异性分子变化及其与酒精使用障碍相关性的有用模型的有效性。
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