substance-p-(4-11)--pro(4)-trp(7-9-10)- and Morphine-Dependence

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.

Topics: Analgesics; Animals; Behavior, Animal; Female; Guinea Pigs; Injections, Intraventricular; Locomotion; Male; Morphine; Morphine Dependence; Motor Activity; Naloxone; Peptide Fragments; Substance P; Substance Withdrawal Syndrome; Tachykinins