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.