Inhibition of Rho kinase by GSK 269962 reverses both corticosterone-induced detrusor overactivity and depression-like behaviour in rats

Wróbel, Andrzej; Serefko, Anna; Rechberger, Ewa; Bańczerowska‐Górska, Małgorzata; Poleszak, Ewa; Dudka, Jarosław; Skorupska, Katarzyna; Miotła, Paweł; Semczuk, Andrzej; Kulik-Rechberger, Beata; Mańdziuk, Sławomir; Rechberger, Tomasz

doi:10.1016/j.ejphar.2018.08.027

Cited by 17 publications

(24 citation statements)

References 39 publications

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“…Repeated injections of corticosterone have been used for years as an animal model of depression in rats ( Iijima et al, 2010 ) and mice ( Zhao et al, 2008 ). We successfully refined this model in our lab ( Wrobel et al, 2016 ; Wrobel et al, 2018 ).…”

Section: Methodsmentioning

confidence: 99%

“…The control animals received a volume-matched injection of the vehicles (saline and/or methyl acetate). The doses of injected drugs as well as the pretreatment schedules were selected on the basis of the published data ( Gratzke et al, 2009 ) and results of our previous studies ( Wrobel et al, 2016 ; Wrobel et al, 2018 ).…”

Section: Methodsmentioning

confidence: 99%

“…The surgical procedures were carried out in the same way as had been previously described ( Wrobel et al, 2016 ; Wrobel et al, 2018 ). The abdominal wall was opened with a vertical midline incision of approximately 10 mm.…”

Section: Methodsmentioning

confidence: 99%

“…According to the literature data ( Cannon and Damaser, 2001 ), ketamine in combination with xylazine does not abolish the micturition reflex in female rats. We also have successfully used this popular method of anaesthesia for years [e.g., ( Wrobel et al, 2015 ; Wrobel et al, 2016 ; Wrobel and Rechberger, 2017 ; Wrobel et al, 2018 )].…”

Section: Methodsmentioning

confidence: 99%

“…The outcomes of our previous projects confirmed that a 14-day exposure to corticosterone generates both depressive phenotype and symptoms of detrusor overactivity in female rats and that these effects are devoid of histopathological damages in the urinary bladder ( Wrobel et al, 2016 ). Moreover, the corticosterone model makes possible to assess signs of inflammation and disturbances in concentrations of neurotrophic factors, which are specific to depression and detrusor dysfunctions ( Wrobel et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

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O-1602, an Agonist of Atypical Cannabinoid Receptors GPR55, Reverses the Symptoms of Depression and Detrusor Overactivity in Rats Subjected to Corticosterone Treatment

et al. 2020

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In view of the fact that GPR55 receptors are localized in brain areas implicated in the pathophysiology of depression, GPR55 gene expression is reduced in the dorsolateral prefrontal cortex of suicide victims, and GPR55 receptor agonism exerts an anxiolytic-like effect, GPR55 receptors have drawn our attention as a potential target in the treatment of mood disorders. Therefore, in the present study, we wanted to check whether a 7-day intravenous administration of O-1602 (0.25 mg/kg/day) – a phytocannabinoid-like analogue of cannabidiol that belongs to the agonists of GPR55 receptors, was able to reverse the corticosterone-induced depressive-like behavior accompanied by detrusor overactivity in female Wistar rats. Additionally, we tried to determine the influence of GPR55 stimulation on the bladder, hippocampal and urine levels of several biomarkers that play a role in the functioning of the urinary bladder and/or the pathophysiology of depression. Our experiments showed that O-1602 therapy improved signs of depression (measured by the forced swim test) and detrusor contractility (measured by conscious cystometry) in animals exposed to the corticosterone treatment. Moreover, the treatment reduced the oxidative damage in the urinary bladder and neuroinflammation (observed as the reduction of elevated levels of 3-NIT, MAL, and IL-1β, TNF-α, CRF, respectively). The O-1602 treatment also reversed the abnormal changes in the bladder, hippocampal or urine values of CGRP, OCT3, VAChT, BDNF, and NGF. The above-mentioned findings allow to suggest that in the future the modulation of atypical cannabinoid receptors GPR55 could have a potential role in the treatment of depression and overactive bladder.

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