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

Abstract

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. The effects on cystometrography of intracerebroventricular atropine, oxybutynin, tolterodine and darifenacin were investigated in normal conscious rats. 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. 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.