Duloxetine reverses the symptoms of overactive bladder co-existing with depression via the central pathways

Pharmacol Biochem Behav. 2020 Feb:189:172842. doi: 10.1016/j.pbb.2019.172842. Epub 2019 Dec 31.

Abstract

Though the association between overactive bladder (OAB) and depression was noticed years ago, the pharmaceutical market does not offer one universal drug that would cure both conditions at the same time. The main goal of our present experiments was to determine whether a 14-day administration of solifenacin (0.03 mg/kg/day), mirabegron (1 mg/kg/day), or duloxetine (1 mg/kg/day) would reverse detrusor overactivity and depression-like signs in female Wistar rats subjected to corticosterone treatment. Surgical procedures, cystometric studies, biochemical analyses, and the forced swim test were performed according to published literature. After 14 days of exposure to corticosterone (20 mg/kg/day, subcutaneously), the tested animals presented symptoms of depression, detrusor overactivity, inflammation, and disturbances in neurotrophic factors. The obtained results demonstrated that solifenacin and mirabegron act mainly via peripheral pathways in OAB, whereas the central pathways are responsible for the effects of duloxetine. 72 h after discontinuation of duloxetine treatment, positive changes in the corticosterone-induced depression, detrusor overactivity, and inflammation were observed. Duloxetine seems to have a potential to become a new treatment option for patients with OAB co-existing with depression.

Keywords: Depression; Detrusor overactivity; Duloxetine; Mirabegron; Rats; Solifenacin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetanilides / administration & dosage
  • Animals
  • Antidepressive Agents / administration & dosage*
  • Behavior, Animal / drug effects
  • Corticosterone / adverse effects
  • Depression / chemically induced
  • Depression / complications*
  • Depression / drug therapy*
  • Disease Models, Animal
  • Duloxetine Hydrochloride / administration & dosage*
  • Female
  • Locomotion / drug effects
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects*
  • Solifenacin Succinate / administration & dosage
  • Thiazoles / administration & dosage
  • Treatment Outcome
  • Urinary Bladder, Overactive / chemically induced
  • Urinary Bladder, Overactive / complications*
  • Urinary Bladder, Overactive / drug therapy*
  • Urological Agents / administration & dosage

Substances

  • Acetanilides
  • Antidepressive Agents
  • Thiazoles
  • Urological Agents
  • Duloxetine Hydrochloride
  • Solifenacin Succinate
  • mirabegron
  • Corticosterone