大鼠侧脑室慢性注射CRF致抑郁样变化研究

为了探讨CRF在抑郁症发生发展过程中的作用．对正常大鼠侧脑室慢性注射CRF21天并与慢性非预见性应激刺激21天建立的抑郁症模型大鼠进行比较。运用旷场行为实验（open-field）观察大鼠主动性活动能力．用Morris water Maze法．以训练期的逃避潜伏期为指标检测大鼠空间学习记忆能力。采用HPLC—UV法测定血清皮质醇含量，RT—PCR法检测CRF及其受体mRNA的表达。结果显示：慢性应激21天建立的模型大鼠主动性活动和学习记忆能力均明显下降．血清皮质醇含量显著升高，CRF及其受体R1 mRNA的表达增加。大鼠侧脑室慢性注射CRF21天后．其体重增量、主动性活动和学习记忆能力与慢性应激模型大鼠一样均明显降低。这些工作证明了CRF在抑郁症的发生发展过程中发挥了至关重要的作用．慢性应激导致机体CRF分泌持续增加可能是抑郁症发病的主要原因。

CHRONIC ADMINISTRATION OF CRF MAKES DEPRESSION LIKE CHANGES IN RATS

For studying the role of CRF in the process of depression, chronic intra-cerebral ventricular administration of CRF in normal rats for 21 days were performed and compared with the depression model of chronic unpredictable miled stress （CUMS） in rats. The Open-field Test and Morris water Maze were employed to test the ability of locomotion and learning and memory. HPLC-UV, RT-PCR were employed to analyze the level of blood serum cortisol and the expression of CRF as well as its receptors （R1 and R2） of CUMS models. After chronic stress, the locomotion activity and spatial learning and memory ability decreased obviously, while the level of serum cortisol increased evidently, and the CRF and its receptor-1 mRNA levels were higher compared with those in normal rats. The rats with chronic administration of CRF also consistently decreased the weight gain, locomotion activity and the ability of spatial learning and memory as the CUMS model. This work demonstrates that CRF plays a very important role in the depression genesis and development, sustained elevation of CRF induced by stress may be the chief factor for depression.