Oitzl M S, Fluttert M, de Kloet E R
Leiden/Amsterdam Centre for Drug Research, University of Leiden, The Netherlands.
Eur J Neurosci. 1994 Jul 1;6(7):1072-9. doi: 10.1111/j.1460-9568.1994.tb00604.x.
Corticosterone, secreted by the adrenal glands, binds to central mineralocorticoid receptors with high affinity and to glucocorticoid receptors with a tenfold lower affinity. In previous studies we have shown that the selective activation of either mineralocorticoid receptors or glucocorticoid receptors exerts distinctly different behavioural effects. In this study we examined in particular the mineralocorticoid receptor-mediated effect of corticosterone on the control of the behavioural response of male Wistar rats to spatial novelty. This analysis was based on our observation that in adrenal-intact rats the presence of an object in the centre of an open field alters the time spent and distance walked in the centre compared to the peripheral area, i.e. the pattern of reactive locomotor activity is changed. Using this paradigm we found that 1 day after removal of the adrenals the rats increased their behavioural reactivity towards the object. Treatment of adrenalectomized rats with a low dose of corticosterone (50 micrograms/kg s.c.) 1 h prior to testing restored the behavioural reactivity to the level of sham-operated, intact rats. Surprisingly, a high dose of corticosterone (1000 micrograms/kg s.c.) also increased the rat's reactivity towards the object. The same high dose of corticosterone given to adrenal-intact rats also increased behavioural reactivity. Pretreatment of these rats with an intracerebroventricular injection of the selective mineralocorticoid receptor antagonist RU28318 (100 ng/microliters) prevented the corticosterone-induced increase in behavioural reactivity, while the blockade of glucocorticoid receptors with the antagonist RU38486 (100 ng/microliters) was not effective. Administration of the mineralocorticoid receptor antagonist without corticosterone to adrenal-intact rats also increased behavioural reactivity, but this increase did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)
由肾上腺分泌的皮质酮，以高亲和力与中枢盐皮质激素受体结合，与糖皮质激素受体的结合亲和力则低10倍。在先前的研究中，我们已经表明，盐皮质激素受体或糖皮质激素受体的选择性激活会产生明显不同的行为效应。在本研究中，我们特别研究了皮质酮通过盐皮质激素受体介导的对雄性Wistar大鼠对空间新奇性的行为反应控制的影响。该分析基于我们的观察结果，即在肾上腺完整的大鼠中，与周边区域相比，旷场中央存在一个物体时，大鼠在中央区域花费的时间和行走的距离会发生改变，即反应性运动活动模式发生了变化。使用这种范式，我们发现摘除肾上腺1天后，大鼠对物体的行为反应性增加。在测试前1小时用低剂量皮质酮（50微克/千克，皮下注射）治疗肾上腺切除的大鼠，可将行为反应性恢复到假手术的完整大鼠水平。令人惊讶的是，高剂量的皮质酮（1000微克/千克，皮下注射）也增加了大鼠对物体的反应性。给肾上腺完整的大鼠注射相同高剂量的皮质酮也增加了行为反应性。用选择性盐皮质激素受体拮抗剂RU28318（100纳克/微升）脑室内注射预处理这些大鼠，可防止皮质酮诱导的行为反应性增加，而用拮抗剂RU38486（100纳克/微升）阻断糖皮质激素受体则无效。给肾上腺完整的大鼠注射盐皮质激素受体拮抗剂而不注射皮质酮也会增加行为反应性，但这种增加未达到统计学显著性。（摘要截短于250字）
