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Vol. 285, Issue 1, 22-27, April 1998
Department of Pharmacology, University of Pittsburgh School of
Medicine, Pittsburgh, Pennsylvania
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 pons to record
field potentials which were evoked by electrical stimulation of the
pelvic nerve (PLN) (1-15 V, 0.05 ms pulse duration at 100-300 Hz,
5-30 ms train duration). The effects of glutamate receptor antagonists
administered intrathecally (i.t.) on the PLN-evoked field potentials in
the dorsal part of the rostral brainstem were examined. PLN stimulation
evoked short latency (10-22 ms) negative field potentials (85 ± 4 µV) in a limited area of the dorsal part of the rostral pons
(bregma 
9.0 to 8.4, L 0.5 to 1.5, H 4.2 to 5.4). The i.t.
administration of LY215490 (0.1-30 µg), a competitive
-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor
antagonist, reduced the amplitude of 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 µg of LY215490, respectively.
The i.t. administration of MK-801 (1-100 µg), a noncompetitive
N-methyl-D-aspartate (NMDA) receptor antagonist, also
reduced the amplitude of the evoked potentials in a dose-dependent
manner; 93 ± 21%, 76 ± 14%, 52 ± 9% (P < .001), 39 ± 9% (P < .001) of control after 1, 10, 30, 100 µg of MK-801, respectively. Combined administration of LY215490 (0.1 µg) and MK-801 (1 µg), in doses which individually did not elicit a
significant effect, markedly reduced the amplitude of the evoked
potentials (27 ± 9% of control, P = .0002). These results suggest that AMPA and NMDA glutamatergic synaptic mechanisms play a key
role in the spinal processing of afferent input from the bladder and
that these mechanisms function synergistically in the ascending limb of
the spinobulbospinal micturition reflex pathway.
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