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

We examined the acute expression of c-Fos or Zif/268 by simultaneous activa tion of N-methyl-D-aspartate receptor and neurokinin-l receptor of the trig eminal nucleus caudalis in anesthetized rats. A selective N-methyl-D-aspart ate receptor agonist, N-methyl-D-aspartate, and/or a selective neurokinin-l 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 wer e counted, Ipsilateral c-Fos and Zif/268 were increased significantly dose- dependently by N-methyl-D-aspartate (at 136 and 340 mu M, and at 68, 136 an d 340 mu M, respectively). On the contralateral side, only Zif/268 increase d significantly (at 68, 136 or 340 mu M). These increases were abolished by D-2-amino-5-phosphonovaleric acid (at 25 mM), a selective N-methyl-D-aspar tate receptor antagonist. Substance P (at 3.7 or 7.4 mu M) significantly in creased dose-dependently ipsilateral c-Fos and Zif/268. On the contralatera l side, only c-Fos was significantly increased (at 3.7 and 7.4 mu M). These increases were abolished by D-2-amino-5-phosphonovaleric acid (at 25 mM) a nd L-703,606 (at 10 mu M), a selective neurokinin-1 receptor antagonist. Th e combined application of N-methyl-D-aspartate 340 mu M + substance P (at 0 .74 or 3.7 mu M) significantly increased ipsilateral c-Fos compared to eith er agent alone. Combined application of N-methyl-D-aspartate 340 mu M + sub stance P at 0.74, 3.7 or 7.4 mu M significantly increased ipsilateral Zif/2 68 expression compared to either drug alone. Other combinations did not inc rease c-Fos and Zif/268. Our results indicate that activation of N-methyl-D-aspartate or neurokinin- l receptor of the trigeminal nucleus caudalis contributes to the acute indu ction of both c-Fos and Zif/268 on the ipsilateral superficial layer of thi s nucleus and simultaneous activation of both receptors by their agonists w ith specific concentrations produces a marked expression of these proteins. Simultaneous activation of N-methyl-D-aspartate and neurokinin-l receptors under some specific conditions may augment synaptic transmission, contribu ting to long-term neuronal change. (C) 2000 IBRO, Published by Elsevier Sci ence Ltd. All rights reserved.