High vs low anxiety-related behavior rats: An animal model of extremes in trait anxiety
High vs low anxiety-related behavior rats: An animal model of extremes in trait anxiety
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DOI：
10.1023/a:1020258104318
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发表时间：
2002-09-01
影响因子：
2.6
通讯作者：
Wigger, A
中科院分区：
文献类型：
--
作者：
Landgraf, R;Wigger, A
除了他们强大的特质焦虑的差异，如各种行为测试所示，HAB和LAB大鼠不同的压力应对策略，前者更容易受到压力暴露，更喜欢被动的策略。HAB大鼠的性别显示出高反应性的下丘脑-垂体-肾上腺皮质（HPA）轴的迹象，因此类似于精神病患者。原位杂交和微透析显示，在自由行为的动物，无论是在下丘脑室旁核的加压素的表达和释放HAB高于LAB大鼠，从而有助于HPA轴超驱动。因此，在HAB动物中，给予V1受体拮抗剂使地塞米松/促肾上腺皮质激素释放激素试验的病理结果正常化，并引发行为变化，减少焦虑和积极应对压力。药理学验证揭示了抑郁样行为的迹象，因为HAB而不是LAB大鼠在用帕罗西汀治疗后显示出更积极的压力应对行为和正常化的HPA轴。有趣的是，这种抗抑郁药减少了下丘脑加压素的过度表达;这种新的作用机制可能有助于帕罗西汀对行为和神经内分泌参数的影响。交叉交配和交叉培养的范例表明，不同的情绪在HAB与LAB大鼠是由遗传决定的，而不是出生后通过母亲的行为。由于行为和神经内分泌表型指出加压素基因作为一个候选基因，严重参与焦虑，初步的遗传学方法已集中在这个基因，揭示单核苷酸多态性（SNP）的加压素基因的启动子区域在HAB，但不是LAB大鼠。因此，HAB/LAB大鼠被证明是一个独特的动物模型，以确定和表征神经生物学，神经内分泌和遗传相关的特质焦虑，也许抑郁症，在人类。
In addition to their robust difference in trait anxiety, as illustrated by a variety of behavioral tests, HAB and LAB rats differ in their stress coping strategies, the former being more susceptible and vulnerable to stressor exposure and preferring more passive strategies. HAB rats of either gender show signs of a hyper-reactive hypothalamic-pituitary-adrenocortical (HPA) axis, thus resembling psychiatric patients. As shown by in situ hybridization and microdialysis in freely behaving animals, both the expression and release of vasopressin in the hypothalamic paraventricular nucleus are higher in HAB than in LAB rats, thus contributing to the HPA axis hyperdrive. Accordingly, in HAB animals, administration of a V1 receptor antagonist normalized the pathological outcome of the dexamethasone/corticotropin-releasing hormone test and triggered behavioral changes toward reduced anxiety and active stress coping. Pharmacological validation has revealed signs of depressive-like behavior, as HAB but not LAB rats have shown more active stress coping behavior and a normalized HPA axis after treatment with paroxetine. Of interest, this antidepressant reduced the hypothalamic overexpression of vasopressin; this novel mechanism of action is likely to contribute to paroxetine effects on both behavioral and neuroendocrine parameters. Cross-mating and cross-fostering paradigms showed that the divergent emotionality in HAB vs. LAB rats is determined genetically, rather than postnatally through maternal behavior. As the behavioral and neuroendocrine phenotyping pointed to the vasopressin gene as a candidate gene critically involved in anxiety, preliminary genetic approaches have been focused on this gene, revealing single nucleotide polymorphisms (SNPs) in the promotor area of the vasopressin gene in HAB, but not LAB rats. HAB/LAB rats are thus proving to be a unique animal model to identify and characterize neurobiological, neuroendocrine, and genetic correlates of trait anxiety, and perhaps depression, in humans.