van den Buuse Maarten, van Acker Saskia A B E, Fluttert Marc F J, de Kloet E R
Neuropharmacology Laboratory, Baker Medical Research Institute, Prahran, Australia.
Physiol Behav. 2002;75(1-2):207-15. doi: 10.1016/s0031-9384(01)00642-4.
The aim of the present study was to investigate the modulatory action of different concentrations of circulating corticosterone occupying either predominantly mineralocorticoid receptors (MR) or both MR and glucocorticoid receptors (GR) in control of cardiovascular responses to a novelty stressor. Six groups of rats were instrumented with radiotelemetry transmitters: sham-operated controls, adrenalectomised (ADX) controls, ADX with chronic implantation of a 20-mg corticosterone pellet, ADX with chronic implantation of a 100-mg corticosterone pellet, ADX receiving acute bolus injection of 0.25 mg/kg of corticosterone, and ADX with both implantation of a 20-mg corticosterone pellet and bolus treatment. Exposure to the novelty of an open field caused an increase in blood pressure, heart rate, body temperature and exploratory locomotor activity. The pressor response was dose-dependently increased in ADX rats implanted with a corticosterone pellet. Bolus injection of corticosterone at 10 min prior to novelty had no effect. The tachycardia was reduced in ADX rats compared to sham-operated controls, and this effect was restored by implantation of a 20-mg, but not 100-mg, corticosterone pellet. Bolus injection of corticosterone facilitated the return of heart rate towards baseline levels. The increase in body temperature was reduced in ADX rats, a deficit that was normalised by implantation of either corticosterone dose but not by acute bolus treatment. Locomotor activity was not different between the groups except for a slightly more rapid decline of locomotor activity in both groups treated with a bolus injection of corticosterone. These data show an important role of putative brain MR in maintaining adequate cardiovascular and behavioural responsiveness to a mild psychological stressor, while additional acute or chronic occupation of GR has further differential and sometimes opposing effects.
本研究的目的是调查不同浓度的循环皮质酮主要占据盐皮质激素受体(MR)或同时占据MR和糖皮质激素受体(GR)时,对心血管系统应对新异应激源反应的调节作用。将六组大鼠植入无线电遥测发射器:假手术对照组、肾上腺切除(ADX)对照组、慢性植入20 mg皮质酮丸剂的ADX大鼠、慢性植入100 mg皮质酮丸剂的ADX大鼠、接受0.25 mg/kg皮质酮急性推注的ADX大鼠,以及既植入20 mg皮质酮丸剂又进行推注治疗的ADX大鼠。暴露于空旷场地的新异环境中会导致血压、心率、体温和探索性运动活动增加。在植入皮质酮丸剂的ADX大鼠中,升压反应呈剂量依赖性增加。在新异刺激前10分钟推注皮质酮没有效果。与假手术对照组相比,ADX大鼠的心动过速有所降低,植入20 mg而非100 mg皮质酮丸剂可恢复这种效应。推注皮质酮有助于心率恢复至基线水平。ADX大鼠的体温升高有所降低,植入任何一种皮质酮剂量均可使其恢复正常,但急性推注治疗则不能。除了两组接受皮质酮推注治疗的大鼠运动活动下降略快外,各组之间的运动活动没有差异。这些数据表明,假定的脑MR在维持对轻度心理应激源的适当心血管和行为反应方面具有重要作用,而GR的额外急性或慢性占据具有进一步的差异效应,有时甚至是相反的效应。