Lack of the development of morphine tolerance in experimental amnesia: role of arginine vasopressin.
The development of tolerance to morphine analgesia in amnesic model mice and the role of arginine vasopressin (AVP) in the underlying mechanism was examined. Hypoxia, brain ischemia, scopolamine and electroconvulsive shock (ECS) manipulation caused amnesia in the step-through type passive avoidance learning test performed at 24 h after the training trial. The amnesic state lasted for at least 3 days and recovered to naive control level on the 20th day after each manipulation. In all amnesic groups, radioimmunoassayable AVP content in hypothalamus was decreased, in particular, the reduction was significant in hypoxia and ischemic induced amnesic animals, then recovered to the control level by 20 days after each treatment. Daily morphine, 10 mg/kg, s.c. easily resulted in the development of tolerance to the analgesic effect in control animals; however, such treatment failed to develop tolerance in amnesic model animals, leaving the analgesic effect unchanged to the control levels. Daily pretreatment with i.c.v. AVP, dose-dependently reinstated the development of tolerance in amnesic model mice. When morphine injection was started from 20 days after the amnesia inducing treatment, tolerance developed as in a similar pattern as in control animals. Thus, amnesic model mice are deficient in brain AVP levels, and consequently, a certain level of AVP in the hypothalamus is required for maintaining the normal function such as the development of tolerance to morphine and the recovery from amnesia.
Sugimachi
N
N
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Nagasaki University, Japan.
Nakamura
T
T
Takahashi
M
M
Kaneto
H
H
D000647:Amnesia / Q000139:chemically induced / Q000523:psychology*; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000008:administration & dosage / Q000378:metabolism / Q000502:physiology*; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D002545:Brain Ischemia / Q000523:psychology; D004361:Drug Tolerance; D004597:Electroshock; D002534:Hypoxia, Brain / Q000523:psychology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000494:pharmacology*; D012601:Scopolamine
D000700:Analgesics; D001127:Arginine Vasopressin; D009020:Morphine; D012601:Scopolamine