Spinally-mediated behavioural responses evoked by intrathecal high-dose morphine: possible involvement of substance P in the mouse spinal cord.
Intrathecal (i.t.) administration of morphine in the spinal subarachnoid space of mice produced a severe hindlimb scratching followed by biting and licking. The onset of the scratching behaviour was observed 60-70 s after i.t. injection of morphine (60 and 90 nmol), and had a duration of 3-4 min. The morphine-induced behaviour was increased additively by i.t. co-administration of substance P (SP). This characteristic behavioural response was inhibited dose-dependently by i.t. co-administration of the tachykinin NK-1 receptor antagonists, sendide and CP-96,345. Significant antagonistic effects of SP (1-7), a putative antagonist for NK-1 receptors and [D-Phe7, D-His9]SP (6-11), a selective antagonist for SP receptors, were observed against the morphine-induced behaviour. Pretreatment with i.t. SP antiserum and i.t. capsaicin resulted in reduction of the response to morphine. I.t. administration of somatostatin (SOM) antiserum, cysteamine, a relatively selective depletor of SOM and cyclo-SOM, a SOM receptor antagonist, produced no inhibitory effect on the morphine-induced behaviour. These results demonstrate that a spinal system of neurones containing SP may be involved in elicitation of the behavioural episode following i.t. injection of morphine in mice.
Sakurada
T
T
Department of Biochemistry, Daiichi College of Pharmaceutical Sciences, Fukuoka, Japan.
Wako
K
K
Sakurada
C
C
Manome
Y
Y
Tan-no
K
K
Sakurada
S
S
Kisara
K
K
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology; D003538:Cystamine / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology*; D013004:Somatostatin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013116:Spinal Cord / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D015320:Tachykinins / Q000008:administration & dosage / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D006727:Hormone Antagonists; D009292:Narcotic Antagonists; D009294:Narcotics; D015320:Tachykinins; D013373:Substance P; D013004:Somatostatin; D009020:Morphine; D003538:Cystamine; D002211:Capsaicin