Involvement of substance P and excitatory amino acids in aversive behavior elicited by intrathecal capsaicin.
The rat given an intrathecal injection of capsaicin (0.3-10 nmol/rat) through a lumbar puncture showed biting or licking the tail and hind paws. The substance P antagonist, CP-96,345 (3 nmol/rat), co-administered intrathecally with capsaicin (10 nmol/rat), caused a significant inhibition of the behavioral responses to capsaicin (10 nmol/rat). When co-administered intrathecally with the NMDA antagonist, 2-amino-5-phosphonovaleric acid (APV, 10 nmol/rat), the capsaicin (10 nmol/rat) -induced behavioral responses were significantly inhibited. A co-administration of the non-NMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 nmol/rat), resulted in a significant reduction of the behavioral responses produced by capsaicin (10 nmol/rat). Administration of the combination of two antagonists (CP-96,345 and either APV or CNQX, or APV and CNQX) more markedly inhibited the behavioral responses to capsaicin (10 nmol/rat) than when either antagonist was co-administered with capsaicin. The results suggest that aversive behaviors induced by intrathecal capsaicin are mediated not only by the activation of NK-1 receptors but also by that of NMDA and non-NMDA receptors.
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; D000596:Amino Acids / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D001713:Biphenyl Compounds / Q000494:pharmacology; D002211:Capsaicin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates / Q000502:physiology; D018698:Glutamic Acid; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012054:Reinforcement, Psychology; D013373:Substance P / Q000037:antagonists & inhibitors / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D000596:Amino Acids; D001713:Biphenyl Compounds; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D006993:Hypnotics and Sedatives; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D013373:Substance P; D018698:Glutamic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D002211:Capsaicin; C066892:CP 96345