Effects of MK-801 and CNQX, glutamate receptor antagonists, on bladder activity in neonatal rats

This study was undertaken to examine the role of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) glutamatergic receptors in the regulation of urinary bladder activity in the neonatal rat. Experiments were conducted using an in vitro spinal cord-bladder (SB) preparation from 1- to 5-day-old rats or awake neonatal rats 6 and 7 days old. SB preparations were isolated under hypothermic anesthesia. Isovolumetric bladder contractions occurred spontaneously, were induced by electrical stimulation (ES) of the bladder wall or were evoked reflexly by perineal tactile stimulation (PS). MK-801 (3-30 microM), an NMDA receptor antagonist, enhanced the amplitude of spontaneous, ES- and PS-evoked contractions. Removal of the spinal cord after MK-801 abolished PS-evoked reflex contractions but did not change the amplitude of spontaneous and ES-evoked contractions. Removal of the spinal cord in the absence of MK-801 increased the amplitude of spontaneous and ES-evoked contractions, indicating that the bladder is subject to a tonic inhibitory control originating in the spinal cord. 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 3-30 microM), an AMPA receptor antagonist, decreased the amplitude of PS-evoked contractions and the frequency of spontaneous contractions in the SB preparation. Removal of the spinal cord after CNQX enhanced the amplitude of spontaneous and ES-evoked contractions but abolished PS-evoked contractions. The frequency of spontaneous contractions which decreased after CNQX increased to near control levels after removal of the spinal cord. In awake neonatal rats, intraperitoneal injection of MK-801 (3 mg/kg) induced spontaneous micturition. A large dose of CNQX (30 mg/kg) decreased PS-evoked micturition volume. These results suggest that NMDA glutamatergic receptors are involved in a lumbosacral spinal inhibitory mechanism controlling bladder activity; whereas AMPA glutamatergic receptors are involved in the perineal-to-bladder reflex pathway in neonatal rats.