Wróbel Andrzej, Rechberger Ewa, Rechberger Tomasz
Second Department of Gynecology, Medical University of Lublin, Jaczewskiego 8, PL 20-090, Lublin, Poland.
Int Urogynecol J. 2018 Jul;29(7):987-995. doi: 10.1007/s00192-017-3424-2. Epub 2017 Jul 31.
The aim of this study was to assess the efficacy of duloxetine in an animal model of detrusor overactivity induced by depression.
After 6 weeks of 13-cis-retinoic acid administration at a dose of 1 mg/kg/day, rats were given duloxetine at a dose of 1 mg/kg. This was followed by conscious cystometry, a forced swim test, and locomotor activity measurement. The levels of corticotropin-releasing factor (CRF) in the hypothalamus, amygdala and plasma were also determined.
Duloxetine treatment led to a reduction in detrusor overactivity symptoms induced by the retinoid. Decreases were observed in cystometric parameters including the detrusor overactivity index, and the amplitude and frequency of nonvoiding contractions, while increases were seen in bladder compliance and the volume threshold to elicit nonvoiding contractions. No statistically significant differences were found in basal pressure, threshold pressure, micturition voiding pressure, postvoid residual , volume threshold, voiding efficiency, intercontraction interval, bladder contraction duration or relaxation time. Duloxetine also reduced the immobility time to that observed in control animals, while it did not affect locomotor activity. Its effects also included lowering of the CRF levels in the hypothalamus, amygdala and plasma, which increased following the prior administration of the retinoid. The plasma level of 13-cis-retinoic acid in rats corresponded to the levels found in humans.
This is the first study showing the efficacy of duloxetine in an animal model of detrusor overactivity induced by depression. Further studies in patients with detrusor overactivity and coexisting depression are warranted to confirm these experimental results.
本研究旨在评估度洛西汀在抑郁症诱导的逼尿肌过度活动动物模型中的疗效。
以1 mg/kg/天的剂量给予大鼠13-顺式维甲酸6周后，再给予1 mg/kg的度洛西汀。随后进行清醒膀胱测压、强迫游泳试验和运动活动测量。还测定了下丘脑、杏仁核和血浆中促肾上腺皮质激素释放因子（CRF）的水平。
度洛西汀治疗可减轻类视黄醇诱导的逼尿肌过度活动症状。膀胱测压参数有所下降，包括逼尿肌过度活动指数、非排尿收缩的幅度和频率，而膀胱顺应性和引发非排尿收缩的容量阈值有所增加。在基础压力、阈值压力、排尿压力、排尿后残余尿量、容量阈值、排尿效率、收缩间期、膀胱收缩持续时间或舒张时间方面未发现统计学显著差异。度洛西汀还将不动时间缩短至对照动物的水平，同时不影响运动活动。其作用还包括降低下丘脑、杏仁核和血浆中的CRF水平，在先前给予类视黄醇后这些水平有所升高。大鼠血浆中13-顺式维甲酸的水平与人类中发现的水平相当。
这是第一项显示度洛西汀在抑郁症诱导的逼尿肌过度活动动物模型中疗效的研究。有必要对逼尿肌过度活动且并存抑郁症的患者进行进一步研究以证实这些实验结果。
