Login to Access Video or Poster Abstract: MP94-08
Sources of Funding: None

Introduction

The modulatory actions of glutamate, the main excitatory neurotransmitter in the central nervous system, are exerted via activation of metabotropic glutamate receptors (mGluRs). Eight distinct mGluRs (mGluR1-8) have been classified into three groups (I-III) based on their sequence homology. Group III mGluRs (mGluRIII; mGluR4, mGluR6, mGluR7 and mGluR8) are widely distributed throughout the central nervous system. However, it is unknown whether mGluRIII plays a role in the regulation of neural mechanisms controlling the micturition reflex. In the present study, we assessed whether L-(+)-2-amino-4-phosphonobutyric acid (L-AP4), a selective mGluRIII agonist, affects the micturition reflex in urethane-anesthetized rats.

Methods

Adult female Sprague-Dawley rats weighing 238 to 261 g were used. Continuous cystometrograms (CMG, 0.04 ml/min infusion rate) were performed in two groups of urethane-anesthetized rats. A group of 24 rats was used for intracerebroventricular administration of 1-10 µg of L-AP4 via a catheter inserted into the lateral ventricle. Using a stereotaxic micro-injector, a 30 gauge needle attached to a 10 µl Hamilton syringe was inserted into the lateral ventricle and single doses of drugs were administered in a volume of 2 µl during 2 minutes. In the second group of 24 rats, 1-10 µg of L-AP4 were administered intrathecally via an intrathecal catheter. Intrathecal injections were made through a polyethylene-10 (PE-10) catheter positioned at the level of the L6-S1 spinal cord. A PE-10 intrathecal catheter was implanted using isoflurane anesthesia 3 days before the experiments. Cystometric parameters were recorded and compared before and after drug administration.

Results

Intracerebroventricular administration of L-AP4 at doses of 1, 3 and 10 μg (n=8 per dose) increased intercontraction intervals in a dose dependent fashion to 117.1 ± 12.3%, 132.5 ± 10.5% and 137.1 ± 15.6% of the control value, respectively (p <0.01), but did not affect residual urine or baseline pressure at any of the doses tested. Intrathecal administration of L-AP4 at doses of 1, 3 and 10 μg (n=8 per dose) also increased intercontraction intervals in a dose dependent fashion to 125.3 ± 8.2%, 136.9 ± 7.1% and 142.7 ± 12.6% of the control value, respectively (p <0.01), but did not affect residual urine or baseline pressure at any of the doses tested.

Conclusions

The results of our study indicate that in urethane-anesthetized rats activation of mGluRIII can inhibit the micturition reflex at supraspinal and spinal sites. Thus, mGluRIII could be a potential target for the treatment of bladder dysfunction, such as overactive bladder.

Funding

None