Kõks S, Männistö P T, Bourin M, Shlik J, Vasar V, Vasar E
Department of Physiology, University of Tartu, Estonia, Männistö.
J Psychiatry Neurosci. 2000 Jan;25(1):33-42.
To examine the influence of pre-experimental stress on the anxiogenic-like action of caerulein, an agonist of cholecystokinin (CCK) receptors. Differences in the anxiety levels of rats in summer and winter, and the role of CCK in these behavioural alterations, were also examined.
Prospective animal study.
Male Wistar rats were injected with the CCK agonist caerulein, or the CCK antagonists L-365,260 or devazepide, after being exposed to pre-experimental stress (handling and isolation).
Performance in the plus-maze model of anxiety; serum levels of prolactin, thyrotropin and growth hormone; brain density and affinity of dopamine D2, serotonin 5-HT2 and CCK receptors.
Caerulein (5 micrograms/kg, subcutaneous injection) caused the strongest action in animals brought to the experimental room immediately before the experiment and kept in isolation after the administration of caerulein. Caerulein did not cause any reduction of exploratory activity in rats made familiar with the experimental room and kept in the home-cage after the injection of the CCK agonist. The anti-exploratory action of caerulein in stressed rats was reversed by the CCK antagonist L-365,260 (100 micrograms/kg, intraperitoneal injection), demonstrating the involvement of the CCKB receptor subtype. In addition, seasonal fluctuations occur in the exploratory activity of rats; such activity was much lower in July than in November. The rats displaying the reduced exploratory activity had an increased number of CCK receptors in the frontal cortex and hippocampus. Simultaneously, the density of serotonin 5-HT2 receptors in the frontal cortex, but not that of dopamine D2 receptors in the striatum, was elevated. The blood level of growth hormone was also higher in July.
The anti-exploratory action of caerulein appears to be dependent on the pre-experimental stress of rats. Moreover, the seasonal variations of exploratory behaviour of rats are evident in the plus-maze model of anxiety. The reduced exploratory activity in summer appears to be related to the elevated density of CCK and 5-HT2 receptors in the brain.
研究实验前应激对胆囊收缩素（CCK）受体激动剂蛙皮素致焦虑样作用的影响。同时考察大鼠在夏季和冬季焦虑水平的差异以及CCK在这些行为改变中的作用。
前瞻性动物研究。
雄性Wistar大鼠在经历实验前应激（处理和隔离）后，注射CCK激动剂蛙皮素、CCK拮抗剂L-365,260或地伐西匹。
在焦虑的十字迷宫模型中的表现；血清催乳素、促甲状腺激素和生长激素水平；脑内多巴胺D2、5-羟色胺5-HT2和CCK受体的密度及亲和力。
蛙皮素（5微克/千克，皮下注射）对在实验前即刻被带入实验室且在注射蛙皮素后进行隔离的动物产生最强作用。在注射CCK激动剂后已熟悉实验室并饲养在笼中的大鼠中，蛙皮素未引起探索活动的任何减少。CCK拮抗剂L-365,260（100微克/千克，腹腔注射）可逆转蛙皮素对应激大鼠的抗探索作用，表明CCKB受体亚型参与其中。此外，大鼠的探索活动存在季节性波动；7月的此类活动远低于11月。探索活动降低的大鼠额叶皮质和海马中的CCK受体数量增加。同时，额叶皮质中5-羟色胺5-HT2受体的密度升高，而纹状体中多巴胺D2受体的密度未升高。7月生长激素的血液水平也更高。
蛙皮素的抗探索作用似乎依赖于大鼠的实验前应激。此外，大鼠探索行为的季节性变化在焦虑的十字迷宫模型中很明显。夏季探索活动减少似乎与脑内CCK和5-HT2受体密度升高有关。
