Suppression of detrusor-sphincter dysynergia by GABA-receptor activation in the lumbosacral spinal cord in spinal cord-injured rats.

We investigated the effects of in- trathecal application of GABA_A- or GABA_B-receptor agonists on detrusor-sphincter dyssynergia (DSD) in spinal cord transection (SCT) rats. Adult female Sprague-Dawley rats were used. At 4 wk after Th_9-10 SCT, simultaneous recordings of intravesical pressure and urethral pressure were performed under an awake condition to examine the effect of intrathecal application of GABA_A and GABA_B agonists (muscimol and baclofen, respectively) or GABAA and GABA_B antagonists (bicuculline and saclofen, respectively) at the level of L₆-S₁ spinal cord. In spinal-intact rats, the effects of bicucul-line and saclofen on bladder and urethral activity were also examined. During urethral pressure measurements, DSD characterized by urethral pressure increases during isovolumetric bladder contractions were observed in 95% of SCT rats. However, after intrathecal application of muscimol or baclofen, urethral pressure showed urethral relaxation during isovolumetric bladder contractions. The effective dose to induce inhibition of urethral activity was lower compared with the dose that inhibited bladder contractions. The effect of muscimol and baclofen was antagonized by intrathecal bicuculline and saclofen, respectively. In spinal-intact rats, intrathecal application of bicucul-line induced DSD-like changes. These results indicate that GABA_A- and GABA_B-receptor activation in the spinal cord exerts the inhibitory effects on DSD after SCT. Decreased activation of GABA_A receptors due to hypofunction of GABAergic mechanisms in the spinal cord might be responsible, at least in part, for the development of DSD after SCT. [ABSTRACT FROM AUTHOR]