RT Journal Article SR Electronic T1 Chronopharmacology of Analgesic Effect and Its Tolerance Induced by Morphine in Mice JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 1200 OP 1205 DO 10.1124/jpet.103.049031 VO 305 IS 3 A1 Miyako Yoshida A1 Shigehiro Ohdo A1 Hiroshi Takane A1 Yuki Tomiyoshi A1 Ayaka Matsuo A1 Eiji Yukawa A1 Shun Higuchi YR 2003 UL http://jpet.aspetjournals.org/content/305/3/1200.abstract AB 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. The American Society for Pharmacology and Experimental Therapeutics