Effects of chronic blockade of N-methyl-D-aspartate receptors by MK-801 on neuroplasticity of the micturition reflex pathway after partial urethral obstruction in the rat

Purpose: To determine the role of N-methyl-D-aspartate (NMDA) glutamatergic receptors in the development of functional bladder changes after partial urethral obstruction we investigated the effects of repeat injection of MK-801, a noncompetitive NMDA receptor antagonist, on the micturition reflex in conscious obstructed rats. Materials and Methods: In 9 female Wistar rats 1.0 mg/kg MK-801 was injected intramuscularly once weekly just prior to the creation of partial urethral obstruction until 5 weeks after obstruction. Five to 7 days after the last injection of MK-801 conscious filling cystometry was performed and compared with that in 9 obstructed rats treated with vehicle (saline). Conscious filling cystometry was also compared in 9 and 7 sham operated rats treated with repeat injection of MK-801 and vehicle, respectively. Results: Partial urethral obstruction caused a significant increase in bladder weight. However, chronic MK-801 treatment did not affect bladder weight in obstructed or sham operated rats. In the obstructed/MK-801 vs the obstructed/vehicle group chronic treatment with MK-801 significantly increased bladder capacity (2.29+/-0.12 vs 1.73+/-0.16 ml, p<0.01) and voided volume (2.00±0.10 vs 1.56±0.17 ml, p<0.05) without changes in voiding efficiency (87.5%+/-1.6% vs 87.8%+/-1.7%) or micturition pressure (55.8+/-2.3 vs 56.4+/-3.0 cm water). Interestingly neither the frequency nor amplitude of premicturition contractions during filling was different in the groups. In sham operated rats chronic MK-801 treatment did not change bladder capacity, voided volume, voiding efficiency or micturition pressure significantly. Conclusions: The results in the current study suggest that bladder outlet obstruction causes NMDA receptor mediated alterations in bladder afferent pathways in the rat.