Functional Role of Central Muscarinic Receptors for Micturition in Normal Conscious Rats

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Abstract
Purpose: Antimuscarinic agents, which are used in to treat urgency and urge incontinence, have well-known effects on peripheral muscarinic receptors. However, some currently used drugs may have effects on muscarinic receptors in the brain and/or spinal cord involved in voiding control. We tested if muscarinic receptors within the central nervous system mediate a tonic excitatory influence on voiding in rats and if these receptors can be differently influenced by antimuscarinic drugs. Materials and Methods: The effects on cystometrography of intracerebroventricular atropine, oxybutynin, tolterodine and darifenacin were investigated in normal conscious rats. Results: Atropine (0.2 to 2 nmol.) dose dependently affected urodynamic parameters. At 2 nmol. in 6 rats the drug decreased voiding pressure (p <0.01), and increased bladder capacity (p <0.001), voided volume (p <0.05) and post-void residual volume (p <0.05). In 6 rats oxybutynin (6 to 40 nmol.) given at a dose of 6 nmol. caused no change in cystometric parameters, while at 20 nmol. the drug decreased voiding pressure (p <0.01). Tolterodine (2 to 20 nmol.) dose dependently changed urodynamic parameters, while at 20 nmol. in 6 rats the drug decreased voiding pressure (p <0.01) and increased bladder capacity (p <0.05) and voided volume (p <0.05). Darifenacin given at a dose of 20 nmol. in 6 rats caused no change in cystometric parameters. Conclusions: Muscarinic receptor mechanisms in the central nervous system mediate a tonic excitatory influence on voiding in rats, while nonsubtype selective antimuscarinic drugs may have an inhibitory effect on these mechanisms