The effect of glutamate antagonists on c-fos expression induced in spinal neurons by irritation of the lower urinary tract.
Chemical irritation of the lower urinary tract (LUT) of the rat increases the expression of c-fos in neurons in the dorsal horn, dorsal commissure and intermediolateral region of the spinal cord. The role of glutamatergic synapses in this response was examined using two glutamate receptor antagonists, MK-801 (an NMDA antagonist) and CNQX (an AMPA antagonist). In rats with an intact spinal cord, MK-801 (3.5 mg/kg, i.v.) administered 15 min before bladder irritation decreased (50-60%) the number of c-fos-positive cells in all regions of the cord. A smaller dose of MK-801 (0.8 mg/kg, i.v.) was ineffective. In spinal transected rats (4-7 days prior to the experiment) MK-801 (3.5 mg/kg, i.v.) decreased c-fos expression only in the medial dorsal horn. CNQX (1.2 mg/kg, i.v.) was ineffective in both preparations. These results indicate that activation of NMDA receptors at glutamate synapses in the central nervous system may play a role in the processing of nociceptive input from the LUT and may also be involved in reflex pathways mediating micturition.
Department of Pharmacology and Behavioral Neuroscience, University of Pittsburgh School of Medicine, PA 15261.
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Birder
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de Groat
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D003655:Decerebrate State; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D016762:Genes, fos / Q000235:genetics*; D005971:Glutamates / Q000502:physiology; D018698:Glutamic Acid; D007509:Irritants / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects*; D014551:Urinary Tract / Q000187:drug effects*
D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D007509:Irritants; D018377:Neurotransmitter Agents; D011810:Quinoxalines; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione