Effects of γ-Aminobutyrate B Receptor Modulation on Normal Micturition and Oxyhemoglobin Induced Detrusor Overactivity in Female Rats

No AccessJournal of UrologyINVESTIGATIVE UROLOGY1 Dec 2002Effects of γ-Aminobutyrate B Receptor Modulation on Normal Micturition and Oxyhemoglobin Induced Detrusor Overactivity in Female Rats RIKARD PEHRSON, ANDERS LEHMANN, and KARL-ERIK ANDERSSON RIKARD PEHRSONRIKARD PEHRSON More articles by this author , ANDERS LEHMANNANDERS LEHMANN More articles by this author , and KARL-ERIK ANDERSSONKARL-ERIK ANDERSSON More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)64247-4AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Using baclofen (Sigma-Aldrich, Steinheim, Germany), a γ-aminobutyrate B (GABA(B)) receptor agonist, and CGP62349 (AstraZeneca R & D Mölndal, Sweden), a GABA(B) receptor antagonist, in a rat model of conscious micturition we addressed certain questions, including whether there is a tonic GABA(B) receptor influence on normal bladder function, how baclofen affects normal and C-fiber activated micturition, and where the sites of GABA(B) receptor action are. Materials and Methods: Nonanesthetized female Sprague-Dawley rats were used. The bladder was catheterized and other catheters were placed intravenously, intrathecally or intracerebroventricularly. At 3 days the rats underwent cystometric investigation in a metabolic cage. Micturition was stimulated by infusing saline intravesically. Overactivity caused by C-fiber activation was induced by intravesical oxyhemoglobin. Drugs were given intravenously, intrathecally or intracerebroventricularly. Micturition parameters were recorded and compared before and after drug administration Results: Baclofen at doses of 0.5 μg. intrathecally and 0.3 μg. intracerebroventricularly increased bladder capacity and threshold pressure. Overflow incontinence developed in 4 of 7 rats after 0.5 μg. baclofen intrathecally and in 5 of 7 after 1 μg. baclofen intracerebroventricularly. CGP62349 at a dose of 30 μg. intrathecally and intracerebroventricularly had a stimulatory effect on micturition, which was attenuated by baclofen. While intravenous baclofen at 1 mg. kg.−1 was devoid of effects, intravenous baclofen at 4 mg. kg.−1 tended to decrease micturition pressure, bladder capacity and micturition volume. Infusion volume decreased significantly, demonstrating a diuretic effect, which was abolished by pretreatment with subcutaneous desmopressin at 25 ng. kg.−1. CGP62349 at 2 mg. kg.−1 intravenously had a stimulatory effect on micturition, which was inhibited by baclofen. Intravesical oxyhemoglobin at 250 μM. induced bladder overactivity, which was attenuated by baclofen at 4 mg. kg.−1 intravenously and abolished by baclofen 0.5 μg intrathecally. Conclusions: In the normal rat stimulation of GABA(B) receptors, mainly in the central nervous system, inhibits micturition. 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