反复给予咖啡因会加重大鼠创伤后应激障碍样症状。

Repeated caffeine administration aggravates post-traumatic stress disorder-like symptoms in rats.

机构信息

Neurotherapeutics Laboratory, Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221 005, U.P., India.

出版信息

Physiol Behav. 2019 Nov 1;211:112666. doi: 10.1016/j.physbeh.2019.112666. Epub 2019 Aug 31.

DOI:10.1016/j.physbeh.2019.112666

PMID:31479682

Abstract

BACKGROUND

Caffeine is the widely consumed central nervous system stimulant in form of coffee and other beverages. However, the repeated administration of caffeine induces anxiety, disturbance in hypothalamic-pituitary-adrenal (HPA) axis and psychiatric symptoms in humans. As much evidence links PTSD to HPA axis dysfunction, and anxiety is a hallmark symptom, repeated and/or large doses of caffeine may exacerbate symptoms of PTSD.

OBJECTIVE

In our present study, we evaluated the effect of repeated administration of caffeine on stress re-stress (SRS) model of PTSD.

METHODS

As per the protocol, male rats were restrained for 2 h followed by 20 min forced swim and halothane anaesthesia on day 2 (D-2). Then the rats were re-stressed (forced swim) at 6-days interval between D-8 to D-32. After exposure to SRS, depressive, anxiety-like behaviour, and cognitive functions were evaluated by forced swim test (FST), elevated plus maze (EPM) and Y-maze tests respectively. Caffeine (10, 20 and 30 mg/kg, i.p.) dosing was started from D-8 and continued up to D-32. The corticosterone level was measured in plasma followed by serotonin and glucocorticoid receptor (GR) and mineralocorticoid receptors (MR) estimation in hippocampus (HIP), prefrontal cortex (PFC) and amygdala (AMY).

RESULTS

SRS-induced depressive and anxiety-like behaviour was aggravated by caffeine at dose of 20 and 30 mg/kg. Caffeine (30 mg/kg) treated control animals showed depressive, anxiety-like behaviour and cognitive impairments. SRS-induced decrease in plasma corticosterone level and increase in serotonin (5HT) levels in the PFC, HIP and AMY were not altered by caffeine. Caffeine did not modulate the SRS-induced decrease in glucocorticoid receptor (GR) and mineralocorticoid receptor (MR). In contrast, caffeine per se decreased GR and MR expression and their ratio in unstressed animals.

CONCLUSION

Repeated intake of caffeine aggravates PTSD-like symptoms in stress-exposed rats and induces PTSD-like symptoms in unstressed rats by altering the expression of glucocorticoid receptors.

摘要

背景

咖啡因是一种广泛存在于咖啡和其他饮料中的中枢神经系统兴奋剂。然而，重复给予咖啡因会导致人类出现焦虑、下丘脑-垂体-肾上腺（HPA）轴紊乱和精神症状。由于大量证据表明创伤后应激障碍与 HPA 轴功能障碍有关，而焦虑是其标志性症状，因此重复和/或大剂量的咖啡因可能会加重创伤后应激障碍的症状。

目的

在本研究中，我们评估了重复给予咖啡因对创伤后应激障碍（PTSD）SRS 模型的影响。

方法

根据方案，雄性大鼠在第 2 天（D-2）接受 2 小时的束缚，然后进行 20 分钟的强制游泳和氟烷麻醉。然后，在 D-8 至 D-32 之间的 6 天间隔内对大鼠进行再应激（强制游泳）。暴露于 SRS 后，通过强迫游泳试验（FST）、高架十字迷宫（EPM）和 Y 迷宫试验分别评估抑郁、焦虑样行为和认知功能。从 D-8 开始给予咖啡因（10、20 和 30mg/kg，腹腔注射），并持续至 D-32。测量血浆中的皮质酮水平，然后测定海马（HIP）、前额叶皮层（PFC）和杏仁核（AMY）中的 5-羟色胺和糖皮质激素受体（GR）和盐皮质激素受体（MR）。

结果

SRS 诱导的抑郁和焦虑样行为在 20 和 30mg/kg 剂量的咖啡因作用下加重。用 30mg/kg 咖啡因处理的对照动物表现出抑郁、焦虑样行为和认知障碍。咖啡因没有改变 SRS 诱导的血浆皮质酮水平降低和 PFC、HIP 和 AMY 中 5-羟色胺（5HT）水平升高。咖啡因没有调节 SRS 诱导的糖皮质激素受体（GR）和盐皮质激素受体（MR）减少。相反，咖啡因本身降低了未应激动物的 GR 和 MR 表达及其比值。