The influence of duloxetine on detrusor overactivity in rats with depression induced by 13-cis-retinoic acid

Abstract

Introduction and hypothesisThe aim of this study was to assess the efficacy of duloxetine in an animal model of detrusor overactivity induced by depression.MethodsAfter 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.ResultsDuloxetine 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.ConclusionsThis 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.

A Comprehensive Review of Overactive Bladder Pathophysiology: On the Way to Tailored Treatment

“…Treatments targeting the bladder or colorectum have been reported to improve or worsen functional disorders in the other organ [92,93], which may support the use of treatments that have been proved to target both the bladder and the bowel in this OAB phenotype, such as SNM or PTNS [97,98]. Recent studies have indicated the potential role of SNM/PTNS in treating IBS in patients with affective disorders [99], and selected data also support the role of SNM/PTNS in treating social stress-induced OAB [32,68,69]. Through this logic, duloxetine may also be a future therapeutic option in the management of patients with "brain-gut-bladder axis-OAB" by targeting central sensitisation.…”

“…Serotonin depletion has been postulated as another shared pathophysiological candidate for both anxiety/depression and OAB, as its role in affective disorders is well established and several experimental studies have demonstrated that lowering of serotonin levels in the CNS was accompanied by urinary frequency and DO [66,67]. Duloxetine, a noradrenalineserotonin reuptake inhibitor, has been reported to improve significantly frequency and urgency in an RCT of female OAB patients [68] and may be a valuable candidate for the treatment of stress-induced OAB, as shown in animal studies [69]. Indeed, it is licensed for the treatment of depression at a lower dose than that studied for the treatment of SUI.…”

Small compounds mimicking the adhesion molecule L1 improve recovery in a zebrafish demyelination model

“…Contrary to tacrine-treated larvae, duloxetine-treated larvae did not show improved functional locomotive recovery. Although duloxetine has been reported to induce hyperactivity in several animal models, other studies have observed deviating effects of this compound [30][31][32] . Duloxetine treatment may affect the behavior of zebrafish larvae via 5-HT4 and α 2 -adrenergic receptors in the central and peripheral nervous system and has been reported to cause a decrease in swimming speed and an increase in resting time, which is consistent with our results 33 .…”

Psychiatric History and Overactive Bladder Symptom Severity in Ambulatory Urogynecological Patients

“…Many peripheral and central neurotransmitters, such as serotonin (5-HT), γ-aminobutyric acid (GABA), and acetylcholine (ACh), are thought to be involved in the pathophysiology of both OAB and psychiatric disorders. These neurotransmitters are also the target for commonly used psychotropic medications [5,[11][12][13][14][15][16]. Animal studies have revealed that lowering serotonin levels in the brain may be accompanied by frequent urination and detrusor overactivity [15,16].…”

“…These neurotransmitters are also the target for commonly used psychotropic medications [5,[11][12][13][14][15][16]. Animal studies have revealed that lowering serotonin levels in the brain may be accompanied by frequent urination and detrusor overactivity [15,16]. Serotonin reduction is also thought to contribute to depression and selective serotonin reuptake inhibitors (SSRIs) are effective in depression treatment [11,12].…”