Murphy D, Costall B, Smythe J W
Postgraduate Studies in Neuropharmacology, Department of Pharmacology, University of Bradford, West Yorkshire, UK.
Brain Res Bull. 1998 Apr;45(6):631-5. doi: 10.1016/s0361-9230(97)00462-0.
Recently, we reported that intrahippocampal cholinergic blockade increased corticosterone (CORT) and adrenocorticotrophin (ACTH) secretion induced by restraint stress. These data suggested to us that CORT may modify hippocampal cholinergic function as part of the negative-feedback control of hypothalamic-pituitary-adrenal (HPA) axis activity. Hippocampal cholinergic theta is a rhythmic, sinusoidal waveform that occurs in alert, immobile rats presented with threatening stimuli and is reliably expressed in urethanized rats. We reasoned that if hippocampal cholinergic systems regulate HPA axis activity, perhaps CORT acts to modulate theta activity. In the present study we have examined the effects of blocking mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) on theta activity in urethane-anesthetized rats. Adult male, Lister hooded rats (n=15) were anesthetized with urethane, and a theta recording electrode was positioned in the hippocampus adjacent to an infusion cannula. A bipolar stimulating electrode was placed in the dorsomedial posterior hypothalamus (DMPH) to activate theta. Baseline recordings of DMPH-stimulated activity (0.1-0.5 mA) were obtained. Rats were then administered either the MR antagonist spironolactone or the GR antagonist RU 38486 (150 ng), and DMPH-stimulated activities were monitored for 45 min. Changes in theta frequency (Hz) and amplitude (mV; energy at peak theta frequency) were analyzed using analysis of variance (ANOVA) followed by Bonferroni t-tests. Neither drug affected hippocampal theta frequencies elicited by DMPH stimulation. However, GR blockade produced marked increases in theta amplitudes of approximately 100% above predrug levels. Alternatively, MR blockade produced exactly the opposite response, as amplitude values fell to approximately 50% of predrug levels. Hippocampal cholinergic theta activity is modulated by CORT acting through MR and GR, and the rapidity of the response suggests a nongenomic mechanism. These data raise the possibility that hippocampal cholinergic systems, and theta activity, are involved in CORT-mediated negative-feedback control of the HPA axis.
最近，我们报道海马体内胆碱能阻断会增加束缚应激诱导的皮质酮（CORT）和促肾上腺皮质激素（ACTH）分泌。这些数据让我们认为，作为下丘脑 - 垂体 - 肾上腺（HPA）轴活动负反馈控制的一部分，CORT可能会改变海马胆碱能功能。海马胆碱能θ波是一种有节律的正弦波形，出现在受到威胁刺激的警觉、静止的大鼠中，并且在氨基甲酸乙酯麻醉的大鼠中可靠地表达。我们推断，如果海马胆碱能系统调节HPA轴活动，那么CORT可能会调节θ波活动。在本研究中，我们研究了阻断盐皮质激素受体（MR）和糖皮质激素受体（GR）对氨基甲酸乙酯麻醉大鼠θ波活动的影响。成年雄性利斯特戴帽大鼠（n = 15）用氨基甲酸乙酯麻醉，将一个θ波记录电极置于靠近输注套管的海马体中。将一个双极刺激电极置于下丘脑背内侧后部（DMPH）以激活θ波。获得DMPH刺激活动（0.1 - 0.5 mA）的基线记录。然后给大鼠施用MR拮抗剂螺内酯或GR拮抗剂RU 38486（150 ng），并监测DMPH刺激活动45分钟。使用方差分析（ANOVA），然后进行Bonferroni t检验，分析θ波频率（Hz）和振幅（mV；θ波峰值频率处的能量）的变化。两种药物均未影响DMPH刺激引起的海马θ波频率。然而，GR阻断使θ波振幅明显增加，比给药前水平高出约100％。或者，MR阻断产生了完全相反的反应，因为振幅值降至给药前水平的约50％。海马胆碱能θ波活动受通过MR和GR起作用的CORT调节，并且反应的快速性表明存在非基因组机制。这些数据增加了海马胆碱能系统和θ波活动参与CORT介导的HPA轴负反馈控制的可能性。
