Simultaneous activation of N-methyl- d-aspartate and neurokinin-1 receptors modulates c-Fos and Zif/268 expression in the rat trigeminal nucleus caudalis

Abstract

We examined the acute expression of c-Fos or Zif/268 by simultaneous activation of N-methyl- d-aspartate receptor and neurokinin-1 receptor of the trigeminal nucleus caudalis in anesthetized rats. A selective N-methyl- d-aspartate receptor agonist, N-methyl- d-aspartate, and/or a selective neurokinin-1 receptor agonist, substance P, was applied topically to the dorsal surface of the spinal trigeminal tract. Immunohistochemically stained nuclei for c-Fos and Zif/268 at laminae I and II of the trigeminal nucleus caudalis were counted. Ipsilateral c-Fos and Zif/268 were increased significantly dose-dependently by N-methyl- d-aspartate (at 136 and 340 μM, and at 68, 136 and 340 μM, respectively). On the contralateral side, only Zif/268 increased significantly (at 68, 136 or 340 μM). These increases were abolished by d-2-amino-5-phosphonovaleric acid (at 25 mM), a selective N-methyl- d-aspartate receptor antagonist. Substance P (at 3.7 or 7.4 μM) significantly increased dose-dependently ipsilateral c-Fos and Zif/268. On the contralateral side, only c-Fos was significantly increased (at 3.7 and 7.4 μM). These increases were abolished by d-2-amino-5-phosphonovaleric acid (at 25 mM) and l-703,606 (at 10 μM), a selective neurokinin-1 receptor antagonist. The combined application of N-methyl- d-aspartate 340 μM+substance P (at 0.74 or 3.7 μM) significantly increased ipsilateral c-Fos compared to either agent alone. Combined application of N-methyl- d-aspartate 340 μM+substance P at 0.74, 3.7 or 7.4 μM significantly increased ipsilateral Zif/268 expression compared to either drug alone. Other combinations did not increase c-Fos and Zif/268. Our results indicate that activation of N-methyl- d-aspartate or neurokinin-1 receptor of the trigeminal nucleus caudalis contributes to the acute induction of both c-Fos and Zif/268 on the ipsilateral superficial layer of this nucleus and simultaneous activation of both receptors by their agonists with specific concentrations produces a marked expression of these proteins. Simultaneous activation of N-methyl- d-aspartate and neurokinin-1 receptors under some specific conditions may augment synaptic transmission, contributing to long-term neuronal change.