The NMDA receptor antagonist MK-801 reduces capsaicin-induced c-fos expression within rat trigeminal nucleus caudalis.
The effect of the N-methyl-D-aspartate (NMDA) receptor antagonist (5R, 10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-i mine hydrogen maleate (MK-801) was examined on c-fos-like immunoreactivity (c-fos-LI) in urethane-anesthetized Sprague-Dawley rats using a polyclonal antibody. C-fos, an indicator of neuronal activation, was assessed within the trigeminal nucleus caudalis (TNC), area postrema. lateral reticular and solitary tract nuclei 2 h after intracisternal injection of capsaicin. C-fos-positive cells were counted at three representative levels corresponding to obex, -2.05 mm and -6.45 mm in 18 tissue sections (50 microm). A weighted average was obtained reflecting total brainstem expression within lamina I, II of TNC using a recently validated method. Capsaicin (0.1, 1, 5, 10 and 15 nmol) caused a dose-dependent labeling of cells in lamina I, II at obex similar to that previously reported after intracisternal blood or carrageenin administration in rats and guinea pigs. MK-801 (0.3, 1 and 3 mg/kg) administered i.p. 30 min before capsaicin (5 nmol in 100 microl artificial CSF) reduced significantly and dose-dependently (12%, 36% and 47%, respectively) the c-fos-LI cells in TNC at each level from rostral to caudal but not in solitary tract, area postrema and lateral reticular nuclei, and for unexplained reasons, increased c-fos-LI within the inferior olive. These results suggest that NMDA receptors provide a potential therapeutic target for cephalic pain (e.g. migraine) due to trigeminovascular activation from meningeal afferents.
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown 02129, USA. mitsikos@helix.mgh.harvard.edu
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Mitsikostas
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Sanchez del Rio
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Waeber
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Moskowitz
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Cutrer
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002211:Capsaicin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002452:Cell Count / Q000187:drug effects; D003864:Depression, Chemical; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013997:Time Factors; D014278:Trigeminal Nuclei / Q000187:drug effects / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D002211:Capsaicin