GABA receptor activation in the lumbosacral spinal cord decreases detrusor overactivity in spinal cord injured rats.
OBJECTIVE
We investigated the effects of intrathecal application of gamma-aminobutyric acid A and B receptor agonists on detrusor overactivity in spinal cord injured rats.


METHODS
Adult female Sprague-Dawley rats were used. At 4 weeks after Th9-10 spinal cord transection awake cystometry and recordings of external urethral sphincter electromyogram were performed to examine the effect of intrathecal application of the gamma-aminobutyric acid A and B agonists muscimol and baclofen or the gamma-aminobutyric acid A and B antagonists bicuculline and saclofen (Tocris Cookson, Ellisville, Missouri), respectively, at the level of the L6-S1 spinal cord. The expression of glutamate decarboxylase 67 mRNA in the L6-S1 spinal cord and dorsal root ganglia was also assessed.


RESULTS
Muscimol and baclofen produced a dose dependent inhibition of the number (51% to 73% decrease) and amplitude (35% to 93% decrease) of nonvoiding bladder contractions and a decrease in micturition pressure. The effects of muscimol and baclofen were antagonized by bicuculline and saclofen, respectively. Bursting activity of external urethral sphincter electromyogram was inhibited, corresponding to the inhibition of bladder activity by muscimol and baclofen. Glutamate decarboxylase 67 mRNA levels in the spinal cord and dorsal root ganglia were decreased after spinal cord transection (55% and 84%, respectively).


CONCLUSIONS
These results indicate that gamma-aminobutyric acid A and B receptor activation in the spinal cord inhibits detrusor overactivity. The decrease in glutamate decarboxylase 67 mRNA suggests hypofunction of GABAergic inhibitory mechanisms in the spinal cord. Therefore, stimulation of spinal GABAergic mechanisms could be effective for the treatment of detrusor overactivity after spinal cord injury.
Miyazato
Minoru
M
Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Sasatomi
Kurumi
K
Hiragata
Shiro
S
Sugaya
Kimio
K
Chancellor
Michael B
MB
de Groat
William C
WC
Yoshimura
Naoki
N
D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000031:analogs & derivatives; D001640:Bicuculline / Q000008:administration & dosage; D004195:Disease Models, Animal; D005260:Female; D018755:GABA Agonists / Q000008:administration & dosage*; D018756:GABA Antagonists / Q000008:administration & dosage; D005968:Glutamate Decarboxylase / Q000096:biosynthesis; D007278:Injections, Spinal; D008159:Lumbar Vertebrae; D009118:Muscimol / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000378:metabolism*; D012447:Sacrum; D013116:Spinal Cord / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D014563:Urodynamics / Q000187:drug effects
D018755:GABA Agonists; D018756:GABA Antagonists; D018079:Receptors, GABA; D009118:Muscimol; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D001418:Baclofen; C080629:saclofen; D001640:Bicuculline