Cholecystokinin tetrapeptide effects on HPA axis function and elevated plus maze behaviour in maternally separated and handled rats
Cholecystokinin tetrapeptide effects on HPA axis function and elevated plus maze behaviour in maternally separated and handled rats
复制标题
DOI：
10.1016/j.bbr.2005.02.006
复制
发表时间：
2005-06-20
影响因子：
2.7
通讯作者：
Wörtwein, G
中科院分区：
文献类型：
--
作者：
Greisen, MH;Bolwig, TG;Wörtwein, G
下丘脑-垂体-肾上腺（HPA）轴的功能缺陷被认为是抑郁症和焦虑症的易感因素。这反映在动物模型“母体分离（MS）”中，其中在出生后早期发育期间大鼠幼仔与母体重复分离的应激导致HPA轴功能的长期持续改变。胆囊收缩素增加大鼠血清应激轴激素的浓度，并可能参与母鼠-幼鼠的相互作用。因此，我们假设，成年动物，这已被分开，每天（出生后（PND）2-14）180分钟（MS 180）将不同的HPA轴的反应，以静脉内的胆囊收缩素四肽（CCK-4）的挑战剂量相比，处理大鼠，每天分开15分钟。本研究探讨了静脉注射CCK-4对高架十字迷宫行为和HPA轴激素的影响。MS 180动物在高架十字迷宫中表现出一般活动减少，但开放臂活动水平不变。给予CCK-4可增加处理大鼠的一般活动，而MS 180大鼠则不受影响。MS 180大鼠下丘脑室旁核中CRF mRNA表达增加。当在长期导管植入和单独饲养的大鼠中评估CRF mRNA时，与处理的动物相比，MS 180动物的室旁核中发现较低的水平，并且该参数不受CCK-4处理的影响。MS 180和处理大鼠血清中促肾上腺皮质激素浓度相等，不受CCK-4影响。与盐水处理的处理大鼠相比，盐水处理的MS 180大鼠中皮质酮血清浓度较低。注射CCK-4可使MS 180大鼠血清皮质酮水平升高至与处理组大鼠相当，而处理组大鼠不受影响。我们认为MS 180大鼠下丘脑CRF mRNA水平和血清皮质酮浓度较低可能是由于慢性静脉导管植入和单一住房的实验设置。总之，本研究支持假设升高CCK敏感性在分离大鼠皮质酮的变化，从而增加了现有的文献报道的早期生活压力有长期影响HPA轴功能。(c)2005年由Elsevier B. V.出版
Deficits in the function of the hypothalamic-pituitary-adrenal (HPA) axis have been suggested to predispose to the development of depression and anxiety disorders. This is mirrored in the animal model "Maternal Separation (MS) where the stress of repeated separation of rat pups from the dam during early postnatal development results in long lasting alterations in HPA axis function. Cholecystokinin increases serum concentrations of stress axis hormones and might be involved in the dam-pup interaction in rats. Therefore, we hypothesized that adult animals, which had been separated daily (postnatal days (PND) 2-14) for 180 min (MS180) would differ in HPA axis responsiveness to an intravenous challenge dose of cholecystokinin tetrapeptide (CCK-4) compared to handled rats, separated for 15 min daily. The study explored the effects of intravenous CCK-4 on elevated plus maze behaviour and HPA axis hormones. MS 180 animals displayed reduced general activity but unaltered levels of open arm activity in the elevated plus maze. CCK-4 administration elevated general activity in the handled rats, while leaving MS 180 rats unaffected. MS 180 rats had increased baseline CRF mRNA expression in the paraventricular nucleus of the hypothalamus. When CRF mRNA was assessed in chronically catheter implanted and single housed rats, lower levels were found in the paraventricular nucleus of MS 180 animals compared to handled animals and this parameter was not affected by CCK-4 treatment. Adrenocorticotropin concentrations in serum were equal in MS 180 and handled rats and unaffected by CCK-4. Corticosterone serum concentrations were lower in saline treated MS 180 rats compared to saline treated handled rats. CCK-4 injection raised serum corticosterone in MS 180 rats to levels equal to the handled rats, while leaving handled rats unaffected. We suggest that the lower levels of hypothalamic CRF mRNA and serum corticosterone concentrations in MS 180 rats might be due to the experimental set-up with chronic venous catheter implants and single housing. In conclusion, this study supports the hypothesis of elevated CCK sensitivity in separated rats as measured by corticosterone changes thus adding to the existing literature reporting early life stress having long-term impact on HPA axis function. (c) 2005 Published by Elsevier B.V.