Tachykinin antagonists inhibit the morphine withdrawal response in guinea-pigs.
This study was an investigation of the effects of the tachykinin antagonists, spantide and (D-Pro4, D-Trp7,9,10)substance P 4-11, injected intracerebroventricularly (ICV), on the locomotor and behavioural responses of guinea-pigs to substance P (SP) injected ICV and to naloxone-induced morphine withdrawal. SP, 50 nmol, produced increased locomotor activity and behaviour that mimicked the response induced by injection of naloxone hydrochloride, 15 mg/kg, in guinea-pigs treated 2 h previously with morphine sulphate, 15 mg/kg. Spantide or (D-Pro4, D-Trp7,9,10)SP4-11, 10 nmol, reduced the locomotor and behavioural responses to SP and to morphine withdrawal. The results support the suggestion that SP or a related tachykinin might be a mediator of the opioid withdrawal response in the central nervous system as has been proposed for the enteric nervous system.
Johnston
P A
PA
Neuropharmacology Laboratory, Faculty of Medicine, University of Newcastle, N.S.W., Australia.
Chahl
L A
LA
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D007276:Injections, Intraventricular; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D009021:Morphine Dependence / Q000188:drug therapy; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D013373:Substance P / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*; D015320:Tachykinins / Q000037:antagonists & inhibitors*
D000700:Analgesics; D010446:Peptide Fragments; D015320:Tachykinins; D013373:Substance P; D009270:Naloxone; D009020:Morphine; C040436:substance P (4-11), Pro(4)-Trp(7,9,10)-; C042867:spantide