The anxiolytic sertraline reduces the impact of psychological stress on bladder function in mice

West, Eliza G.; Sellers, Donna; Chess-Williams, Russ; McDermott, Catherine

doi:10.1016/j.lfs.2021.119598

Cited by 6 publications

(9 citation statements)

References 53 publications

(65 reference statements)

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“…Nerve mediated bladder responses to EFS, at all frequencies, were not affected by stress or recovery despite a general increase in contractility seen with stress. However when normalised to the KCl response, nerve-evoked contractions were depressed in the stressed group as reported previously [ 3 ], but not in the recovery group. With no change observed in the relative contribution of ATP and ACh to neurotransmission in the bladder, these changes would suggest reduced neurotransmitter release with stress and recovery of these changes post-stress.…”

Section: Discussionsupporting

confidence: 83%

“…Water avoidance stress was performed as previously described [ 2 , 3 ]. Briefly, mice in both the Stressed and Stressed + Recovery groups were placed individually on a pedestal surrounded by water for 1 hour/day for 10 consecutive days (typically started at 11am immediately following voiding analysis).…”

Section: Methodsmentioning

confidence: 99%

“…This is supported by evidence from experimental studies using various rodent models of psychological stress which have shown that stress plays a causal role in the development of bladder dysfunction. Our research group and others has shown that an overactive voiding phenotype develops in female mice and rats following water avoidance stress, with increased urinary frequency evident in voiding behaviour studies [ 1 – 3 ]. This contrasts with the urinary retention seen in male mice due to repeated bouts of social defeat but not witness trauma or restraint stress [ 4 , 5 ] and male rats following water avoidance stress [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Partial recovery of voiding function in female mice following repeated psychological stress exposure

et al. 2022

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Psychological stress causes bladder dysfunction in humans and in rodent models, with increased urinary frequency and altered contractile responses evident following repeated environmental stress exposure. However, whether these changes persist after removal of the stressor is unknown, and the aim of this study was to determine if stress-induced changes in voiding behaviour and bladder function recover following removal of the stressor. Adult female mice were allocated to three groups: Unstressed, Stressed or Stressed + Recovery. Animals in the stressed groups were exposed to water avoidance stress for 1h/day for 10-days, with unstressed animals age-matched and housed under normal conditions. For recovery studies, animals were housed without stress exposure for an additional 10-days. Voiding behaviour was assessed periodically and animals sacrificed on day 10 (Unstressed and Stressed) or day 20 (Unstressed and Stressed + Recovery). Isolated whole bladder studies were used to assess compliance, urothelial mediator release and contractile responses. Exposure to stress increased plasma corticosterone levels almost three-fold (P<0.05) but this returned to baseline during the recovery period. Contractile responses of the bladder to carbachol and KCl were also increased following stress, and again fully recovered after a 10-day stress-free period. In contrast, stress increased urinary frequency four-fold (P<0.001), but this did not return fully to baseline during the recovery period. Bladder compliance was unchanged by stress; however, it was increased in the stressed + recovery group (P<0.05). Thus, following a stress-free period there is partial recovery of voiding behaviour, with an increase in bladder compliance possibly contributing to the compensatory mechanisms.

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Section: Discussionsupporting

confidence: 83%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Partial recovery of voiding function in female mice following repeated psychological stress exposure

et al. 2022

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“…Both therapeutics also reduced stress-induced changes in urothelial ACh release and plasma corticosterone levels. The anxiolytic sertraline tested previously was less effective than both mirabegron and solifenacin in managing voiding changes caused by water avoidance stress, with voiding remaining elevated compared to unstressed animals 21 , suggesting that the muscarinic antagonist and β-adrenoceptor agonist may be more promising to test clinically. These results indicate that management of bladder dysfunction caused by psychological stress may benefit from the addition of an antimuscarinic such as solifenacin or a β 3 -adrenoceptor agonist such as mirabegron.…”

Section: Discussionmentioning

confidence: 96%

“…Increased urinary frequency is common among individuals experiencing chronic psychological stress 4 , 20 . Similarly, repeated water avoidance stress causes an overactive voiding phenotype in mice, which is partially reduced by the anxiolytic sertraline 2 , 5 , 21 . Water avoidance stress has long been reported to affect bladder function via alterations to both central and peripheral processes.…”

Section: Discussionmentioning

confidence: 99%

Mirabegron and solifenacin are effective for the management of the increased urinary frequency induced by psychological stress in female mice

West

McDermott

Chess-Williams

et al. 2022

Sci Rep

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Evidence to support the effectiveness of β3-adrenoceptor agonist mirabegron and anti-muscarinic solifenacin in the management of bladder dysfunction caused by psychological stress is lacking. This study investigates whether mirabegron or solifenacin reduces the bladder overactivity caused by water avoidance stress (WAS) in mice. Female mice were exposed to WAS for 1 h/day for 10 days and received either placebo, solifenacin or mirabegron in drinking water. Controls were age-matched without stress exposure. Voiding behaviour and functional isolated whole bladder responses during distension and in response to pharmacological agents and electrical field stimulation was investigated. Urinary frequency was significantly increased following stress. Mice treated with mirabegron or solifenacin displayed significantly fewer voiding events compared to the stressed mice, and voiding frequency in drug-treated animals was comparable to unstressed controls. The maximal contractile responses of bladders to carbachol were significantly enhanced by stress and reduced by mirabegron but not solifenacin. The frequency of phasic bladder contractions following stimulation with carbachol was significantly enhanced following stress and remained elevated in the mirabegron treated group. However, treatment with solifenacin significantly reduced the frequency of phasic contractions to unstressed control levels. Solifenacin and mirabegron are beneficial in reducing the overall voiding dysfunction caused by WAS in mice.

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Efficacy of KPR‐5714, a selective transient receptor potential melastatin 8 antagonist, on chronic psychological stress‐induced bladder overactivity in male rats

Watanabe

Miyazaki

Yumoto

et al. 2023

Neurourology and Urodynamics

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AimsChronic psychological stress aggravates lower urinary tract symptoms. Among others, water avoidance stress is a chronic psychological stressor that plays a causal role in the exacerbation and development of bladder dysfunction in rats. In this report, the effects of KPR‐5714, which is a selective transient receptor potential melastatin 8 (TRPM8) antagonist, on bladder overactivity induced by water avoidance stress were examined.MethodsMale rats were subjected to water avoidance stress for 2 h per day for 10 consecutive days. The effects of water avoidance stress on voiding behavior using metabolic cages and histological bladder changes were investigated in rats. The involvement of bladder C‐fiber afferent on voiding frequency in rats exposed to water avoidance stress was assessed using capsaicin. The effects of KPR‐5714 on storage dysfunction in rats subjected to water avoidance stress were examined.ResultsIn voiding behavior measurements, water avoidance stress‐induced storage dysfunction, causing a decrease in the mean voided volume and increasing voiding frequency. A comparison of bladders from normal rats and rats exposed to water avoidance stress showed no histological differences. Water avoidance stress‐induced bladder overactivity was completely inhibited by pretreatment with capsaicin. KPR‐5714 showed a tendency to increase the mean voided volume and significantly decreased the voiding frequency without affecting the total voided volume in these rats.ConclusionThe results suggest that KPR‐5714 is a promising option for treating chronic psychological stress‐induced bladder overactivity.

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The anxiolytic sertraline reduces the impact of psychological stress on bladder function in mice

Cited by 6 publications

References 53 publications

Partial recovery of voiding function in female mice following repeated psychological stress exposure

Partial recovery of voiding function in female mice following repeated psychological stress exposure

Mirabegron and solifenacin are effective for the management of the increased urinary frequency induced by psychological stress in female mice

Efficacy of KPR‐5714, a selective transient receptor potential melastatin 8 antagonist, on chronic psychological stress‐induced bladder overactivity in male rats

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