Nociceptin-induced scratching, biting and licking in mice: involvement of spinal NK1 receptors.
1. Intrathecal (i.t.) injection of nociceptin at small doses (fmol order) elicited a behavioural response consisting of scratching, biting and licking in conscious mice. Here we have examined the involvement of substance P-containing neurons by using i.t. injection of tachykinin neurokinin (NK)1 receptor antagonists and substance P (SP) antiserum. 2. Nociceptin-induced behavioural response was evoked significantly 5 - 10 min after i.t. injection and reached a maximum at 10 - 15 min. Dose-dependency of the induced response showed a bell-shaped pattern from 0.375 - 30.0 fmol, and the maximum effect was observed at 3.0 fmol. 3. The behavioural response elicited by nociceptin (3.0 fmol) was dose-dependently inhibited by intraperitoneal (i.p.) administration of morphine. 4. The NK1 receptor antagonists, CP-96,345, CP-99,994 and sendide, inhibited nociceptin-induced behavioural response in a dose-dependent manner. A significant antagonistic effect of [D-Phe7, D-His9]SP (6 - 11), a selective antagonist for SP receptors, was observed against nociceptin-induced response. The NK2 receptor antagonist, MEN-10376, had no effect on the response elicited by nociceptin. 5. Pretreatment with SP antiserum resulted in a significant reduction of the response to nociceptin. No significant reduction of nociceptin-induced response was detected in mice pretreated with NKA antiserum. 6. The N-methyl-D-aspartate (NMDA) receptor antagonists, dizocilpine (MK-801) and D(-)-2-amino-5-phosphonovaleric acid (APV) (D-APV), and L-NG-nitro arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, failed to inhibit nociceptin-induced behavioural response. 7. off present results suggest that SP-containing neurons in the mouse spinal cord may be involved in elicitation of scratching, biting and licking behaviour following i.t. injection of nociceptin.
Sakurada
T
T
Department of Biochemistry, Daiichi College of Pharmaceutical Sciences, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511, Japan.
Katsuyama
S
S
Sakurada
S
S
Inoue
M
M
Tan-No
K
K
Kisara
K
K
Sakurada
C
C
Ueda
H
H
Sasaki
J
J
D000374:Aggression / Q000187:drug effects*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D015288:Neurokinin A / Q000037:antagonists & inhibitors; D064729:Neurokinin-1 Receptor Antagonists; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018847:Opioid Peptides / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000187:drug effects*; D011957:Receptors, Opioid / Q000819:agonists*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013373:Substance P / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology; D000097629:Nociceptin
D000701:Analgesics, Opioid; D019138:Antibodies, Blocking; D001713:Biphenyl Compounds; D009020:Morphine; D015288:Neurokinin A; D064729:Neurokinin-1 Receptor Antagonists; D018847:Opioid Peptides; D010880:Piperidines; D018040:Receptors, Neurokinin-1; D011957:Receptors, Opioid; D013373:Substance P; D000097629:Nociceptin; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; C066892:CP 96345