Effects of N-methyl-D-aspartate (dizocilpine) and alpha-amino-3-hydroxy5-methyl-4-isoxazolepropionate (LY215490) receptor antagonists on the voiding reflex induced by perineal stimulation in the neonatal rat

The present study was undertaken to examine the role of alpha-amino-3-hydro xy-5-methyl-4-isoxazolepropionate and N-methyl-D-aspartate glutamate recept ors in the regulation of voiding reflexes induced by perineal stimulation i n the neonatal rat. Four-, six- and 10-day-old awake rats were used in the experiments and perineal stimulation was applied using the tip of a l-ml sy ringe to evoke voiding. Voided volume and residual volume were measured. In 10-day-old rats, LY215490 (3-10 mg/kg, i.p.), a competitive alpha-amino-3- hydroxy-5-methyl-4-isoxazolepropionate receptor antagonist, significantly i nhibited reflex voiding, increasing the residual volume 34-53-fold. A 3 mg/ kg dose decreased the urine release by 55%, whereas 10 mg/kg totally suppre ssed the voiding reflex induced by the perineal stimulation. LY215490 (10 m g/kg, i.p.) produced similar effects in four- and six-day-old rats. Dizocil pine (1-3 mg/kg, i.p.), a non-competitive N-methyl-D-aspartate: receptor an tagonist, also significantly decreased the urine release (62-82%) and incre ased residual volume (180-230-fold). Combined administration of LY215490 (1 mg/kg, i.p.) and dizocilpine (0.3 mg/kg, i.p.) to 10-day-old rats, in dose s that individually had no effect on perineal stimulation-evoked voiding, d epressed voided volume by 65%. These results indicate that, in neonatal rats, glutamatergic transmission i n the spinal cord has an essential role in reflex micturition induced by pe rineal stimulation, and that facilitatory interactions between alpha-amino- 3-hydroxy-5-methyl-4-isoxazolepropionate and N-methyl-D-aspartate glutamate rgic mechanisms are important for voiding, as noted previously in adult rat s. (C) 1999 IBRO. Published by Elsevier Science Ltd.