Effect of long-term oxybutynin administration on c-Fos expression in spinal neurons: inhibition of antimuscarinics on bladder afferents in conscious rats.
OBJECTIVE
To investigate the effect of long-term administration of oxybutynin on afferent input from the bladder by evaluating c-Fos expression in the spinal cord.


METHODS
Using an osmotic pump, long-term administration of oxybutynin (4 weeks) was performed in the rat. The effects of oxybutynin (2 doses) on the urodynamic parameters were determined by continuous cystometry in conscious rats. After cystometry, c-Fos expression in the spinal cord was measured by immunohistochemistry.


RESULTS
The long-term administration of low-dose oxybutynin (0.36 mg/kg/d) significantly increased the micturition interval and bladder capacity, but it did not affect micturition pressure. However, administration of high-dose oxybutynin (3.6 mg/kg/d) significantly decreased the micturition pressure and increased the residual volume. In the rats that received low-dose oxybutynin, the number of c-Fos-positive neurons in the spinal cord was significantly lower than that in controls.


CONCLUSIONS
Administration of low-dose oxybutynin decreased the c-Fos expression induced by continuous infusion of saline into the bladder. This result suggests that the antimuscarinic drug oxybutynin at clinically recommended doses can exert an inhibitory effect on afferent input from the bladder during the storage phase without affecting detrusor contractions.
Haga
Nobuhiro
N
Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan.
Aikawa
Ken
K
Shishido
Keiichi
K
Takahashi
Norio
N
Yanagida
Tomohiko
T
Yamaguchi
Osamu
O
D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D003243:Consciousness; D005260:Female; D008333:Mandelic Acids / Q000008:administration & dosage* / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000008:administration & dosage* / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology*; D013997:Time Factors; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology*
D008333:Mandelic Acids; D018727:Muscarinic Antagonists; D016760:Proto-Oncogene Proteins c-fos; C005419:oxybutynin