EFFECTS OF GABA-RECEPTOR STIMULATION AND BLOCKADE ON MICTURITION IN NORMAL RATS AND RATS WITH BLADDER OUTFLOW OBSTRUCTION

The effects on micturition of the GABA receptor agonists muscimol (selective for GABA(A)-receptors) and baclofen (selective for GABA(B)-receptors), given intrathecally and intra-arterially to unanesthetized rats with and without bladder hypertrophy secondary to outflow obstruction, were studied by continuous cystometry. When given intrathecally in increasing doses, both muscimol (1 to 10 mug.) and baclofen (0.1 to 5 mug.) produced a dose-dependent inhibition of micturition with progressive increases in bladder capacity and residual volume, and a decrease in micturition pressure ending with urinary retention and dribbling incontinence. Generally, the effects were similar in normal rats and rats with bladder hypertrophy. In normal rats, bicuculline (blocking GABA(A)-receptors) decreased bladder capacity and micturition volume, and increased micturition pressure. In both types of rat, the effects of muscimol and baclofen were partly counteracted by bicuculline and saclofen, respectively. In rats with bladder hypertrophy, the amplitude of the spontaneous bladder contractions during filling was significantly increased after administration of muscimol and baclofen. When given intra-arterially in high doses, muscimol (2 to 16 mg./kg.) and baclofen (8 to 16 mg./kg.) produced effects on cystometric parameters and spontaneous bladder contractions similar to those obtained with intrathecal administration. These results suggest that muscimol and baclofen have insignificant peripheral effects on the lower urinary tract, but depress micturition by an effect on the central nervous system. They also suggest that the inhibitory GABA-ergic system does not play a role in the genesis of bladder hyperactivity in rats with outflow obstruction.