Pharmacological evidence for involvement of excitatory amino acids in aversive responses induced by intrathecal substance P in rats.
Rats given an intrathecal injection of substance P (0.3-10 nmol) or any of the excitatory amino acid agonists, N-methyl-D-aspartate (NMDA, 1-10 nmol), kainate (1 and 3 nmol) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA, 0.3-3 nmol), showed biting or licking the hind paws, scratching with the hind paws (only after substance P) and vocalization (only after excitatory amino acid agonists). The intrathecal co-administration of the NMDA antagonist, 2-amino-5-phosphonovaleric acid (APV, 10 nmol), inhibited behavioral responses to NMDA (10 nmol) and substance P (10 nmol) but not to kainate (3 nmol). Co-administration of the non-NMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 nmol), suppressed responses to kainate (3 nmol), AMPA (3 nmol) and substance P (10 nmol) but not to NMDA (10 nmol). Co-administration of the substance P antagonist, CP-96,345 (3 nmol), inhibited the behavioral responses to substance P (10 nmol), but not to NMDA (10 nmol), kainate (3 nmol) and AMPA (3 nmol). The results suggest that the aversive behavior induced by intrathecal NMDA and non-NMDA agonists is mediated by activation of the corresponding glutamate receptors, but not by NK-1 receptors, and that the behavioral action of intrathecal substance P is mediated not only by direct activation of NK-1 receptors but also indirectly by NMDA and non-NMDA receptors for glutamate.
Okano
K
K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Kuraishi
Y
Y
Satoh
M
M
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000494:pharmacology; D007278:Injections, Spinal; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000378:metabolism; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology*
D001713:Biphenyl Compounds; D011810:Quinoxalines; D017470:Receptors, Glutamate; D018040:Receptors, Neurokinin-1; D013373:Substance P; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid; C066892:CP 96345