O'Donovan Sinead, Dalton Victoria, Harkin Andrew, McLoughlin Declan M
Trinity College Institute of Neuroscience,Trinity College Dublin, Dublin 2,Ireland.
School of Pharmacy & Pharmaceutical Sciences & Trinity College Institute of Neuroscience,Trinity College Dublin, Dublin 2,Ireland.
Int J Neuropsychopharmacol. 2014 Sep;17(9):1477-86. doi: 10.1017/S1461145714000200. Epub 2014 Mar 10.
Brief pulse electroconvulsive therapy (BP ECT; pulse width 0.5-1.5 ms) is the most effective treatment available for severe depression. However, its use is associated with side-effects. The stimulus in ultrabrief pulse ECT (UBP ECT; pulse width 0.25-0.3 ms) is more physiological and has been reported to be associated with less cognitive side-effects, but its antidepressant effectiveness is not yet well established. Using electroconvulsive stimulation (ECS), the animal model of ECT, we previously reported UBP ECS to be significantly less effective than well-established BP ECS in eliciting behavioural, molecular and cellular antidepressant-related effects in naïve rats. We have now compared the effects of BP and UBP ECS in an animal model of depression related to exogenous supplementation with the stress-induced glucocorticoid hormone, corticosterone. Corticosterone administration resulted in an increase in immobility time in the forced swim test (FST) (p < 0.01) and decreases in the expression of brain-derived neurotrophic factor (BDNF) (p < 0.05) and glial fibrillary acidic protein (GFAP) (p < 0.001) in the hippocampus and frontal cortex. There was no significant difference in the duration or type of seizure induced by BP (0.5 ms) or UBP (0.3 ms) ECS. UBP ECS proved to be as effective as BP ECS at inducing a behavioural antidepressant response in the FST with a significant decrease (p < 0.001) in immobility seen following administration of ECS. Both forms of ECS also induced significant increases in BDNF protein (p < 0.01) expression in the hippocampus. BP ECS (p < 0.05) but not UBP ECS induced a significant increase in GFAP levels in the hippocampus and frontal cortex. Overall, UBP ECS effectively induced antidepressant-related behavioural and molecular responses in the corticosterone supplementation model, providing the first preclinical data on the potential role of this form of ECS to treat a depression phenotype related to elevated corticosterone.
短脉冲电休克疗法（BP ECT；脉冲宽度0.5 - 1.5毫秒）是治疗重度抑郁症最有效的方法。然而，其使用会产生副作用。超短脉冲电休克疗法（UBP ECT；脉冲宽度0.25 - 0.3毫秒）的刺激更接近生理状态，据报道其认知副作用较少，但尚未充分确定其抗抑郁效果。我们利用电休克刺激（ECS），即ECT的动物模型，之前报道过在未处理的大鼠中，超短脉冲电休克刺激（UBP ECS）在引发行为、分子和细胞层面与抗抑郁相关的效应方面，显著不如成熟的短脉冲电休克刺激（BP ECS）有效。我们现在比较了BP和UBP ECS在与应激诱导的糖皮质激素皮质酮外源性补充相关的抑郁症动物模型中的效果。给予皮质酮导致强迫游泳试验（FST）中的不动时间增加（p < 0.01），并使海马体和额叶皮质中脑源性神经营养因子（BDNF）的表达降低（p < 0.05）以及胶质纤维酸性蛋白（GFAP）的表达降低（p < 0.001）。BP（0.5毫秒）或UBP（0.3毫秒）ECS诱导的癫痫发作持续时间或类型没有显著差异。在FST中，UBP ECS在诱导行为抗抑郁反应方面被证明与BP ECS一样有效，给予ECS后不动时间显著减少（p < 0.001）。两种形式的ECS还都诱导海马体中BDNF蛋白表达显著增加（p < 0.01）。BP ECS（p < 0.05）而非UBP ECS诱导海马体和额叶皮质中GFAP水平显著增加。总体而言，UBP ECS在皮质酮补充模型中有效诱导了与抗抑郁相关的行为和分子反应，为这种形式的ECS治疗与皮质酮升高相关的抑郁表型的潜在作用提供了首个临床前数据。
