EFFECTS OF LY274614, A COMPETITIVE NMDA RECEPTOR ANTAGONIST, ON THE MICTURITION REFLEX IN THE URETHANE-ANESTHETIZED RAT

1 The effects of 3 competitive N-methyl-D-aspartate (NMDA) receptor an tagonists, LY274614, LY233536 and LY235723, on the micturition reflex and external urethral sphincter EMG- activity, were examined either un der isovolumetric conditions or during continuous filling cystometry i n urethane-anaesthetized (1.2 g kg-1, s.c.) rats. 2 Intravenous admini stration of LY274614 (3-30 mg kg-1) inhibited in a dose-dependent fash ion both bladder and sphincter activity in the intact rats. In additio n, the volume threshold for inducing micturition was increased and voi ded volume was decreased. 3 Intrathecal administration of LY274614 (0. 06-30 mug) similarly inhibited bladder and sphincter activity during c ystometry in intact rats. 4 In chronic spinal cord (T6-T8) transected rats LY274614 (0.1-30 mg kg-1, i.v.) did not alter bladder activity un der isovolumetric conditions but decreased the amplitude of micturitio n contractions and sphincter EMG activity during cystometry at a dose of 10-30 mg kg-1. 5 The inhibitory effects of i.v. administration of L Y274614, on bladder and sphincter activity induced by infusion of chem ical irritant (0.1% acetic acid) or saline, were similar; except that a slightly larger dose was needed to inhibit sphincter activity during acetic acid infusion. 6 Peak amplitude of micturition contractions re covered to 50% of control 3 h following i.v. (30 mg kg-1) or i.t. (6 m ug) administration of LY274614. 7 Two other chemically related NMDA an tagonists, LY233536 and LY235723 produced similar but less potent effe cts than LY274614 when given i.v. 8 These data indicate that glutamate rgic transmitter mechanisms at the level of the spinal cord are import ant in modulating bladder activity in the intact animal, but that thes e mechanisms do not contribute to bladder reflexes in the chronic spin al rat. These mechanisms may, however, contribute to sphincter activit y in both intact or chronic spinal rats.