RP 67580, a selective antagonist of neurokinin-1 receptors, modifies some of the naloxone-precipitated morphine withdrawal signs in rats.
In order to clarify the participation of substance P in the expression of opiate withdrawal, we have investigated the effects induced by the new selective neurokinin-1 antagonist RP 67580 on naloxone-induced morphine withdrawal syndrome in rats. Intracerebroventricular administration of RP 67580 elicited a decrease in 7 of the 13 withdrawal signs evaluated. Mastication, salivation and signs related to the motor component of withdrawal (jumping, rearing and locomotor activity) were particularly reduced. One sign, wet dog shakes, was increased, but it was also enhanced by the inactive enantiomer RP 68651. Our results indicate that blockade of NK1 receptors induces a decrease in the expression of naloxone-precipitated morphine abstinence in rats, and support the participation of substance P in the opiate withdrawal response.
Maldonado
R
R
Unité de Pharmacochimie Moléculaire, U 266 INSERM, UA 498 CNRS, Université René Descartes, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
Girdlestone
D
D
Roques
B P
BP
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D054833:Isoindoles; D008297:Male; D009020:Morphine / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology*; D064729:Neurokinin-1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D012016:Reference Values; D013239:Stereotyped Behavior / Q000187:drug effects*; D013373:Substance P / Q000037:antagonists & inhibitors*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology / Q000517:prevention & control*
D000700:Analgesics; D007211:Indoles; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D013373:Substance P; D009270:Naloxone; D009020:Morphine