Intrathecally administered spermine produces the scratching, biting and licking behaviour in mice.
Intrathecal (i.t.) administration of spermine (0.1-10000 fmol), an endogenous polyamine, produced the behavioural response mainly consisting of biting and/or licking of the hindpaw along with a slight hindlimb scratching directed toward the flank in mice, which peaked at 5-15 min and almost disappeared at 30 min after an injection. The behaviour induced by spermine (10 pmol) was dose-dependently inhibited by intraperitoneal injection of morphine (0.125-0.5 mg/kg). The characteristic behaviour was also inhibited dose-dependently by i.t. co-administration of ifenprodil (62.5-4000 pmol), a competitive antagonist of the polyamine recognition site on N-methyl-D-aspartate (NMDA) receptor ion-channel complex, and D(-)-2-amino-5-phosphonovaleric acid (D-APV) (0.5-2 nmol) and 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) (7. 8-500 pmol), the competitive NMDA receptor antagonists, and (5R, 10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,b]cycloheptene-5, 10-imine hydrogen maleate (MK-801) (0.5-4 nmol), an NMDA ion-channel blocker, but not by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA receptor antagonist. Both (2S, 3S)-[cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)-methyl]-1-azabicy clo [2.2.2]octane-3-amine] (CP-96,345), a non-peptidic neurokinin-1 (NK-1) receptor antagonist, and CP-96,344, its inactive 2R,3R enantiomer, inhibited spermine-induced behavioural response in a dose-dependent manner. However, [Tyr(6), D-Phe(7), D-His(9)]-substance P(6-11) (sendide) and [D-Phe(7), D-His(9)]-substance P(6-11), the selective antagonists for NK-1 receptors, were without affecting spermine-induced behaviour. These results indicate that spermine-induced behaviour is mediated through the polyamine recognition site on NMDA receptor ion-channel complex without the involvement of substance P system in the mouse spinal cord.
Tan-No
K
K
Department of Pharmacology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Japan. koichi@tohoku-pharm.ac.jp
Taira
A
A
Wako
K
K
Niijima
F
F
Nakagawasai
O
O
Tadano
T
T
Sakurada
C
C
Sakurada
T
T
Kisara
K
K
D000374:Aggression / Q000187:drug effects*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006614:Hindlimb / Q000502:physiology; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D011537:Pruritus / Q000139:chemically induced* / Q000523:psychology; D013096:Spermine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013997:Time Factors
D000701:Analgesics, Opioid; D018691:Excitatory Amino Acid Antagonists; D064729:Neurokinin-1 Receptor Antagonists; D013096:Spermine; D009020:Morphine