Journal of pharmacological and toxicological methods · 2016
An animal model of detrusor overactivity induced by depression.
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Wróbel Andrzej, Rechberger Tomasz
Аннотация
INTRODUCTION: Depression is frequently found in patients suffering from overactive bladder. The aim of the study was to verify whether the 13-cis-retinoic acid, a synthetic retinoid used in the treatment of acne, which was proven to induce depressive changes in both humans and animals, can cause detrusor overactivity symptoms in conscious rats.
METHODS: In order to assess the 13-cis-retinoic acid impact on the behavioural parameters, after 6weeks of intraperitoneal administration of retinoid in a dose of 1mg/kg/day, a forced swim test and cystometry were performed, and the locomotor activity of animals was assessed. The control group received a mixture of DMSO and physiological saline at a 1:1 ratio.
RESULTS: 13-cis-retinoic acid caused cystometric parameter changes analogous to those observed in people with a urodynamic diagnosis of detrusor overactivity. The retinoid caused also an extension of the immobility time in the forced swim test which is consistent with increased depression-related behaviour, with no impact on the locomotor activity of rats. The intravenous administration of solifenacin succinate in a single dose of 0.03mg/kg turned out to reverse changes in the cystometric parameters modified by 13-cis-retinoic acid treatment. The histopathological analysis of bladders did not show any lesions in the upper layer of the umbrella cells, urothelium or muscles. The retinoid concentration level achieved in the animals tested turned out to be identical to that occurring in humans.
DISCUSSION: 13-cis-retinoic acid can induce detrusor overactivity symptoms that are reversed by solifenacin succinate.
METHODS: In order to assess the 13-cis-retinoic acid impact on the behavioural parameters, after 6weeks of intraperitoneal administration of retinoid in a dose of 1mg/kg/day, a forced swim test and cystometry were performed, and the locomotor activity of animals was assessed. The control group received a mixture of DMSO and physiological saline at a 1:1 ratio.
RESULTS: 13-cis-retinoic acid caused cystometric parameter changes analogous to those observed in people with a urodynamic diagnosis of detrusor overactivity. The retinoid caused also an extension of the immobility time in the forced swim test which is consistent with increased depression-related behaviour, with no impact on the locomotor activity of rats. The intravenous administration of solifenacin succinate in a single dose of 0.03mg/kg turned out to reverse changes in the cystometric parameters modified by 13-cis-retinoic acid treatment. The histopathological analysis of bladders did not show any lesions in the upper layer of the umbrella cells, urothelium or muscles. The retinoid concentration level achieved in the animals tested turned out to be identical to that occurring in humans.
DISCUSSION: 13-cis-retinoic acid can induce detrusor overactivity symptoms that are reversed by solifenacin succinate.