Abstract
The influence of morphine dosing time on analgesic effect after acute or chronic treatment, recovery of analgesic effect after once developed tolerance, and their pharmacological mechanisms were investigated in ICR male mice under a 12-h light/dark cycle (light on from 7:00 AM to 7:00 PM). There was a significant 24-h rhythm in the latency of thermal response at 30 min after morphine injection. The analgesic effect was significantly greater at the dark phase than at the light phase. The rhythmic pattern resembled overall the rhythm occurring in the latency of thermal response under nondrugged state. The absolute value of morphine analgesic effect (the real time spent on the hot-plate) on days 1 and 2 after morphine daily injection was significantly larger after morphine injection at 9:00 PM than after saline injection at 9:00 PM or after morphine injection at 9:00 AM. The recovery from tolerance of analgesic effect was significantly faster at the dark phase than at the light phase. The time-dependent difference in the analgesic effect after chronic treatment or recovery from tolerance is closely related to that in the expression of μ-opioid receptor. The present study suggests that 24-h rhythm of morphine analgesic effect is consistent with 24-h rhythm of μ-opioid receptor expression.
Footnotes
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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DOI: 10.1124/jpet.103.049031.
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This study was funded by Grant-in-Aid for Scientific Research on Priority Areas “Cancer” (15025254, to S.O.), Grant-in-Aid for Scientific Research (C) (13672391, to S.O.), and Grant-in-Aid for Scientific Research (B) (14370784, to S.H. and S.O.) from the Ministry of Education, Culture, Sports, Science and Technology Japan; Grant-in-Aid from the Pharmacological Research Foundation, Tokyo (to S.O.); and Grant-in-Aid from Japan Research Foundation for Clinical Pharmacology (to S.O.).
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ABBREVIATIONS: DAMGO, [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin.
- Received January 29, 2003.
- Accepted February 27, 2003.
- The American Society for Pharmacology and Experimental Therapeutics
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Chronopharmacology of Analgesic Effect and Its Tolerance Induced by Morphine in Mice
