ROLE OF SPINAL GLUTAMATERGIC TRANSMISSION IN THE ASCENDING LIMB OF THE MICTURITION REFLEX PATHWAY IN THE RAT

This study was undertaken to evaluate the role of glutamate receptors at spinal synapses on the ascending limb of the micturition reflex. In urethane-anesthetized female rats, a tungsten electrode was inserted stereotaxically into the dorsal part of the rostral pens to record fie ld potentials which were evoked by electrical stimulation of the pelvi c nerve (PLN) (1-15 V, 0.05 ms pulse duration at 100-300 Hz, 5-30 ms t rain duration). The effects of glutamate receptor antagonists administ ered intrathecally (i.t.) on the PLN-evoked field potentials in the do rsal part of the rostral brainstem were examined. PLN stimulation evok ed short latency (10-22 ms) negative field potentials (85 +/- 4 mu V) in a limited area of the dorsal part of the rostral pens (bregma -9.0 to -8.4, L 0.5 to 1.5, H 4.2 to 5.4). The i.t. administration of LY215 490 (0.1-30 mu g), a competitive lpha-amino-3-hydroxy-5-methylisoxazol e-4-propionic acid (AMPA) receptor antagonist, reduced the amplitude o f the evoked potentials in a dose-dependent manner; 84 +/- 6%, 59 +/- 11% (P < .001), 31 +/- 10% (P < .001), 17 +/- 9% (P < .001) of control after 0.1, 1, 10, 30 mu g of LY215490, respectively. The i.t. adminis tration of MK-801 (1-100 mu g), a noncompetitive N-methyl-oaspartate ( NMDA) receptor antagonist, also reduced the amplitude of the evoked po tentials in a dose-dependent manner; 93 +/- 21%, 76 +/- 14%, 52 +/- 9% (P < .001), 39 +/- 9% (P < .001) of control after 1, 10, 30, 100 mu g of MK-801, respectively. Combined administration of LY215490 (0.1 mu g) and MK-801 (1 mu g), in doses which individually did not elicit a s ignificant effect, markedly reduced the amplitude of the evoked potent ials (27 +/- 9% of control, P = .0002). These results suggest that AMP A and NMDA glutamatergic synaptic mechanisms play a key role in the sp inal processing of afferent input from the bladder and that these mech anisms function synergistically in the ascending limb of the spinobulb ospinal micturition reflex pathway.