Meijer O C, Kortekaas R, Oitzl M S, de Kloet E R
Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Netherlands.
Eur J Pharmacol. 1998 Jun 12;351(1):7-14. doi: 10.1016/s0014-2999(98)00289-1.
Corticosterone influences 5-HT1A receptor-mediated responses in the rat hippocampus in vitro: activation of the high affinity mineralocorticoid receptor suppresses 5-HT1A receptor-mediated hyperpolarization, while subsequent activation of lower affinity glucocorticoid receptors enhances the effect of 5-HT. We have tested whether a similar effect of corticosterone exists in vivo. In intact rats, a systemic injection of the specific 5-HT1A receptor agonist, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), led to increased locomotion and to a less persistent search strategy in the free swim trial of the Morris water maze test. Adrenalectomized rats with a corticosterone-pellet implanted as replacement received an injection of vehicle (predominant mineralocorticoid receptor occupation) or a high dose of corticosterone (both corticosteroid receptor types occupied) 1 h before injection of 8-OH-DPAT. The effect on search strategy, but not on locomotor activity, was less in animals with low corticosterone levels. The results suggest that hippocampal 5-HT1A receptor-mediated responses in vivo are attenuated during predominant activation of the mineralocorticoid receptor and increased after additional transient activation of the glucocorticoid receptor.
皮质酮在体外影响大鼠海马中5-羟色胺1A（5-HT1A）受体介导的反应：高亲和力盐皮质激素受体的激活抑制5-HT1A受体介导的超极化，而随后低亲和力糖皮质激素受体的激活增强5-羟色胺（5-HT）的作用。我们已经测试了皮质酮在体内是否存在类似的作用。在完整大鼠中，全身注射特异性5-HT1A受体激动剂8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT），在莫里斯水迷宫试验的自由游泳试验中导致运动增加和搜索策略持续性降低。植入皮质酮微丸作为替代物的肾上腺切除大鼠在注射8-OH-DPAT前1小时接受载体注射（主要占据盐皮质激素受体）或高剂量皮质酮注射（两种皮质类固醇受体类型均被占据）。皮质酮水平低的动物对搜索策略的影响较小，但对运动活动的影响不大。结果表明，在盐皮质激素受体主要激活期间，体内海马5-HT1A受体介导的反应减弱，而在糖皮质激素受体额外短暂激活后增强。
