Flaisher-Grinberg Shlomit, Overgaard Shauna, Einat Haim
Dept. of Pharmacy Practice and Pharmaceutical Sciences, College of Pharmacy, University of Minnesota, Duluth, USA.
J Neurosci Methods. 2009 Feb 15;177(1):44-50. doi: 10.1016/j.jneumeth.2008.09.018. Epub 2008 Sep 27.
The lack of appropriate animal models for bipolar disorder (BPD) is a major factor hindering the research of its pathophysiology and the development of new drug treatments. In line with the notion that BPD might represent a heterogeneous group of disorders, it was suggested that models for specific domains of BPD should be developed and then integrated. The present study tested sweet solution preference as a rodent model for increased reward seeking, a central component of manic behavior and a possible endophenotype of the disorder. The study identified that Black Swiss mice show high baseline saccharin preference compared with C57bl/6, CBA/J and A/J strains. Sweet solution preference in Black Swiss mice was therefore evaluated across a number of saccharin concentrations, with or without treatment with the mood stabilizers lithium and valproate and the antidepressant imipramine. Results indicated that the structurally dissimilar mood stabilizers lithium and valproate, but not the antidepressant imipramine, reduce sweet solution preference. However, different dosing schedules were needed for the two drugs to induce this effect. These findings support the face and the predictive validity of the sweet solution preference test as an animal model for the elevated reward-seeking domain of mania. As such, this test might be well integrated into a battery of models for different domains of BPD. Such a battery can be effectively utilized to screen new treatments, to distinguish between specific effects of different drugs, and to explore the mechanisms underlying BPD.
双相情感障碍（BPD）缺乏合适的动物模型是阻碍其病理生理学研究和新药治疗开发的主要因素。鉴于BPD可能代表一组异质性疾病的观点，有人提出应开发BPD特定领域的模型，然后进行整合。本研究测试了甜味溶液偏好作为啮齿动物模型，用于研究奖赏寻求增加，这是躁狂行为的核心组成部分，也是该疾病可能的内表型。研究发现，与C57bl/6、CBA/J和A/J品系相比，黑瑞士小鼠表现出较高的基线糖精偏好。因此，在有或没有使用心境稳定剂锂盐和丙戊酸盐以及抗抑郁药丙咪嗪治疗的情况下，对黑瑞士小鼠在多种糖精浓度下的甜味溶液偏好进行了评估。结果表明，结构不同的心境稳定剂锂盐和丙戊酸盐可降低甜味溶液偏好，而抗抑郁药丙咪嗪则无此作用。然而，两种药物需要不同的给药方案才能产生这种效果。这些发现支持了甜味溶液偏好测试作为躁狂症奖赏寻求增加领域动物模型的表面效度和预测效度。因此，该测试可能很好地整合到一系列针对BPD不同领域的模型中。这样一组模型可有效地用于筛选新的治疗方法，区分不同药物的特定作用，并探索BPD的潜在机制。
