Spinally-mediated behavioural responses evoked by intrathecal high-dose morphine: possible involvement of substance P in the mouse spinal cord

• Published in: Brain research Vol. 724; no. 2; pp. 213 - 221
• Main Authors: Sakurada, Tsukasa, Wako, Kenji, Sakurada, Chikai, Manome, Yoichi, Tan-no, Koichi, Sakurada, Shinobu, Kisara, Kensuke
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 17.06.1996; Amsterdam Elsevier; New York, NY
• Subjects: Animals; Behavior, Animal - drug effects; Behavioral psychophysiology; Biological and medical sciences; Capsaicin - administration & dosage; Capsaicin - pharmacology; Cystamine - administration & dosage; Cystamine - pharmacology; Dose-Response Relationship, Drug; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Hormone Antagonists - administration & dosage; Hormone Antagonists - pharmacology; Injections, Spinal; Intrathecal injection; Male; Mice; Mice, Inbred Strains; Morphine; Morphine - administration & dosage; Morphine - antagonists & inhibitors; Morphine - pharmacology; Narcotic Antagonists - administration & dosage; Narcotic Antagonists - pharmacology; Narcotics - administration & dosage; Narcotics - pharmacology; Neurotransmission and behavior; NK-1 receptor antagonist; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Scratch reflex; Somatostatin - administration & dosage; Somatostatin - antagonists & inhibitors; Somatostatin - pharmacology; Spinal cord; Spinal Cord - physiology; Substance P - analogs & derivatives; Substance P - pharmacology; Substance P - physiology; Tachykinins - administration & dosage; Tachykinins - antagonists & inhibitors; NK-1 receptor antagonist; Morphine; Intrathecal injection; Spinal cord; Scratch reflex; NK1 receptor; Substance P; Rodentia; Central nervous system; Licking behavior; Neuropeptide; Intrathecal administration; Vertebrata; Mammalia; Mouse; Animal; Tachykinin
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/0006-8993(96)00319-8

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-Phe 7, d-His 9jSP (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.