title: Zolpidem increases bladder capacity and decreases urine excretion in rats.
abstract: OBJECTIVE
  To clarify the effects of zolpidem, a gamma-aminobutyric acid (GABA)(A) receptor agonist, on bladder function, and urine production, we investigated the effects of zolpidem administration on bladder overactivity induced by cerebral infarction (CI) and on urine excretion increased by water overloading in Wistar rats.
  
  
  METHODS
  CI was induced by left middle cerebral artery occlusion. The effects on bladder function of zolpidem alone or in combination with the GABA(A) receptor antagonist bicuculline, were then examined in the CI rats using cystometry. The antidiuretic effect of zolpidem was investigated in water-loaded and Brattleboro rats (genetically vasopressin-deficient). Blood samples were collected from water-loaded rats to determine the aldosterone level 1 and 6 hr after zolpidem administration.
  
  
  RESULTS
  Zolpidem increased bladder capacity dose-dependently, but had no significant effect on bladder contraction pressure in CI rats. Bicuculline dose-dependently inhibited zolpidem-induced increases in bladder capacity without affecting bladder contraction pressure. Zolpidem dose-dependently decreased the volume of urine excreted in water-loaded and Brattleboro rats. Compared with the control group, zolpidem significantly increased the aldosterone concentration in the plasma of water-loaded rats 1 hr after administration.
  
  
  CONCLUSIONS
  Zolpidem increased bladder capacity via a GABAergic mechanism in CI rats, and suppressed urine excretion via a pathway that was not through activation of vasopressin V(2) receptors in water-loaded and Brattleboro rats. These results suggest that zolpidem may improve nocturia via an increase in bladder capacity and a decrease in urine excretion.
authors.affiliation: Department of Urology, Faculty of Medical Science, University of Fukui, 23-3 Shimoaizuki, Matsuoka, Fukui 910-1193, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokoyama
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Matsuta
authors.forename: Hiroko
authors.initials: H
authors.lastname: Yanai-Inamura
authors.forename: Mai
authors.initials: M
authors.lastname: Watanabe
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Ohtake
authors.forename: Masanori
authors.initials: M
authors.lastname: Suzuki
authors.forename: Masao
authors.initials: M
authors.lastname: Sasamata
mesh_terms: D000450:Aldosterone / Q000097:blood; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002544:Cerebral Infarction / Q000150:complications / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D018755:GABA Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D007275:Injections, Intravenous; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011910:Rats, Brattleboro; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013997:Time Factors; D001743:Urinary Bladder / Q000187:drug effects* / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D014554:Urination / Q000187:drug effects*; D014563:Urodynamics; D000077334:Zolpidem
chemical_list: D018755:GABA Agonists; D018756:GABA Antagonists; D011725:Pyridines; D000450:Aldosterone; D000077334:Zolpidem; D001640:Bicuculline