Urodynamics in a rat neurogenic bladder model with a unilateral electrolytic lesion of the basal forebrain.
OBJECTIVE
To investigate the changes in bladder function in rats with an electrolytic lesion of the right basal forebrain (RBF) and to determine the effects of AH-9700, a novel sigma receptor ligand, on cystometry in RBF-lesioned rats.


METHODS
A lesion was made electrolytically in the RBF of male Wistar rats. At 7 or 8 days after the lesion or sham surgery, continuous cystometry was performed in awake rats. In addition, contractile responses to electrical field stimulation or carbachol were measured in isolated bladder strips, as were the forebrain contents of acetylcholine, monoamine neurotransmitters and their metabolites.


RESULTS
RBF-lesioned rats showed a remarkable increase in voiding frequency, with a decrease in voiding threshold pressure but no change in voiding pressure, compared with sham-operated rats. However, contractile responses in bladder strips isolated from RBF-lesioned rats were no different from those in strips isolated from sham-operated rats. In RBF-lesioned rats, the contents of acetylcholine, dopamine, 4-dihidroxyphenylacetic acid and homovanillic acid were significantly decreased in the right forebrain. AH-9700 dose-dependently decreased the voiding frequency and increased the threshold pressure in RBF-lesioned rats. Anti-muscarinic agents (oxybutynin and propiverine) also decreased the voiding frequency, but their effects were less potent than that of AH-9700.


CONCLUSIONS
The RBF-lesioned rat may be a useful model for the neurogenic bladder of supraspinal origin. Moreover, AH-9700 effectively improves bladder dysfunction in this model.
Shimizu
I
I
Department of Discovery Pharmacology II, Pharmacology Research Laboratories, Drug Research Division, Dainippon Pharmaceutical Co., Ltd, Osaka, Japan. ishimiz1@jhmi.edu
Kawashima
K
K
Ishii
D
D
Oka
M
M
D000818:Animals; D001561:Benzilates / Q000494:pharmacology; D001927:Brain Diseases / Q000150:complications* / Q000503:physiopathology; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D004195:Disease Models, Animal; D005650:Fumarates / Q000494:pharmacology; D008297:Male; D008333:Mandelic Acids / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology; D016548:Prosencephalon / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D001750:Urinary Bladder, Neurogenic / Q000209:etiology / Q000503:physiopathology*; D014563:Urodynamics
D001561:Benzilates; D018680:Cholinergic Antagonists; D005650:Fumarates; D008333:Mandelic Acids; D009281:Naphthalenes; C437044:1-(2-(3,4-dihydro-6,7-dimethyl-2-naphthalenyl)ethyl) pyrrolidine fumarate; C015586:propiverine; C005419:oxybutynin