A method for producing overactive bladder in the rat and investigation of the effects of GABAergic receptor agonists and glutamatergic receptor antagonists on the cystometrogram.
OBJECTIVE
We induced radio frequency (RF) lesions in the neuronal pathway leading from the forebrain to the pontine micturition center (PMC) to produce a rat model of bladder overactivity. We studied the effects of gamma-aminobutyric acid agonists (diazepam and baclofen) and glutamate receptor antagonists (MK-801 maleate and GYKI52466 [1-(4-aminophenyl-D-4-methyl-7,8 methylenedioxy-5H-2,3-benzodiazepine] hydrochloride) on the cystometrogram and developed a possible explanation of the neuronal mechanisms underlying RF lesion induced bladder overactivity.


METHODS
Seven-week-old male Sprague-Dawley rats were anesthetized with sodium pentobarbital and RF lesions were produced in the nuclei basalis. Five days later bladder contractions were induced by infusing fluid into the bladder and cystometrograms were measured in conscious rats.


RESULTS
The micturition interval (MI) in rats subjected to RF lesioning was significantly shorter than that in sham operated control rats. Diazepam (0.1 and 1 mg/kg intraperitoneally), baclofen (1 mg/kg intravenously) and MK-801 (0.1 and 1 mg/kg intravenously) did not change or shortened MI in control rats but it prolonged MI in lesioned rats. GYKI52466 (0.5 and 1 mg/kg intravenously) weakly prolonged MI in lesioned rats.


CONCLUSIONS
We consider that RF lesioning causes interruption of the inhibitory GABAergic neurons that lead from the forebrain to the PMC. This results in the activation of N-methyl-D-aspartate receptors in the PMC that are involved in the facilitation of voiding.
Kontani
Hitoshi
H
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanagawa-machi, Kanazawa, Japan. h-kontani@hokuriku-u.ac.jp
Ueda
Yasuyuki
Y
D000818:Animals; D001418:Baclofen / Q000008:administration & dosage*; D001569:Benzodiazepines / Q000008:administration & dosage*; D003975:Diazepam / Q000008:administration & dosage*; D016291:Dizocilpine Maleate / Q000008:administration & dosage*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage*; D018757:GABA Modulators / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014549:Urinary Incontinence / Q000139:chemically induced*
D018691:Excitatory Amino Acid Antagonists; D018757:GABA Modulators; C061950:GYKI 52466; D001569:Benzodiazepines; D016291:Dizocilpine Maleate; D001418:Baclofen; D003975:Diazepam