Yunnan Key Laboratory of Regenerative Medicine and Stem Cells, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming, Yunnan, People's Republic of China.
Neurotox Res. 2014 Apr;25(3):235-47. doi: 10.1007/s12640-013-9411-6. Epub 2013 Jul 20.
Depression interferes with the human ability to make decisions. Multiple criteria have been adopted for the diagnosis of depression in humans, but no clear indicators are available in animal models to reflect the depressive mood, involving higher cognitive functions. The act of foraging is a species-specific behaviour which is believed to involve the decision-making and higher cognitive functions. We previously established a method to detect the foraging behaviour of rodents, in which our results demonstrated that NMDA and dopamine receptors were involved. Conversely, increased NMDA receptors and reduced dopamine have been reported in depression model rodents. However, we hypothesise that foraging activities may also be impaired in depression. To test the theory, we successfully established a mouse model of depression using the chronic unpredictable mild stress (CUMS) paradigm. Most interestingly, the food foraging activity of mice after CUMS was significantly reduced. In addition, the treatment of anti-depressant fluoxetine reversed most depressive symptoms and reduced glial fibrillary associated protein (GFAP) expression in the hippocampus, but was less effective in the reduction of foraging activities. However, clozapine reversed all symptoms of CUMS-exposed mice including reduction of GFAP expression in the hippocampus and impaired foraging activity. Our findings of GFAP expression as a marker to validate the CUMS protocol provide further validation of our hypothesis, that the reduced food foraging is probably a new behavioural finding of depression in which the serotoninergic system could not be singly involved. Our study suggests that NMDA receptors, serotoninergic and dopaminergic systems are differentially involved in these food foraging behaviours. Our data suggest that the foraging test in rodents can be a useful tool to assess the ability of decision-making in depression.
抑郁症会干扰人类做出决策的能力。人类的抑郁症诊断采用了多种标准，但动物模型中没有反映涉及更高认知功能的抑郁情绪的明确指标。觅食行为是一种特定于物种的行为，据信涉及决策和更高的认知功能。我们之前建立了一种检测啮齿动物觅食行为的方法，结果表明 NMDA 和多巴胺受体参与其中。相反，抑郁症模型啮齿动物中 NMDA 受体增加和多巴胺减少。然而，我们假设觅食活动也可能在抑郁症中受损。为了验证这一理论，我们使用慢性不可预测轻度应激（CUMS）范式成功建立了一种小鼠抑郁症模型。最有趣的是，CUMS 后小鼠的食物觅食活动明显减少。此外，抗抑郁药氟西汀的治疗逆转了大多数抑郁症状，并降低了海马中的神经胶质纤维酸性蛋白（GFAP）表达，但对觅食活动的减少效果较小。然而，氯氮平逆转了暴露于 CUMS 的小鼠的所有症状，包括海马中 GFAP 表达的减少和觅食活动的受损。我们将 GFAP 表达作为验证 CUMS 方案的标志物的发现为我们的假设提供了进一步的验证，即食物觅食减少可能是抑郁症的一种新行为发现，其中 5-羟色胺能系统不能单独参与。我们的研究表明，NMDA 受体、5-羟色胺能和多巴胺能系统在这些食物觅食行为中存在差异。我们的数据表明，啮齿动物的觅食测试可以成为评估抑郁症决策能力的有用工具。
