Effect of a calcium chelator on morphine tolerance development.
To assess the effects of calcium ion chelation on narcotic tolerance development, adult Sprague-Dawley rats were implanted with i.c.v. cannulae connected to osmotic minipumps for continuous infusions of saline or EGTA (2 mumol/24 h) during chronic morphinization by s.c. pellet implantation. Additional rats receiving the same morphine pellet treatment but without minipumps served as non-surgical controls. After 64 h the minipumps and pellets were removed and narcotic tolerance was assessed by the tail-flick technique. A positive analgetic response to an 8.50 mg/kg s.c. dose of morphine sulfate was noted in 6/12 no-minipump controls and 4/9 saline-infused controls. In placebo-treated rats caused no alteration of either baseline tail-flick latencies or in analgetic responsiveness to lower doses of morphine. It is concluded that the enhancement of morphine tolerance by EGTA (a calcium-specific chelator) results from a facilitation of certain adaptive changes of calcium ion disposition that are related to the neurochemical mechanisms of narcotic tolerance and dependence development.
D000700:Analgesics; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002118:Calcium / Q000502:physiology*; D004361:Drug Tolerance; D004533:Egtazic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D005026:Ethylene Glycols / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D009020:Morphine / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats
D000700:Analgesics; D005026:Ethylene Glycols; D004533:Egtazic Acid; D009020:Morphine; D002118:Calcium