The NMDA receptor antagonist MK-801 reduces capsaicin-induced c- fos expression within rat trigeminal nucleus caudalis

Abstract

The effect of the N-methyl- d-aspartate (NMDA) receptor antagonist (5 R,10 S)-(+)-5-methyl-10,11-dihydro-5 H-dibenzo[ a,d]cyclo-hepten-5,10-imine 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 μm). 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 μl 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.