title: Temporal variation in drug interaction between lithium and morphine-induced analgesia.
abstract: The administration-time-dependent aspects of the drug interaction between lithium and morphine-induced analgesia were studied using the mouse hot-plate test at six different times of day, each scheduled at 4 h intervals. Lithium treatment alone, in doses of 1 to 10 mmol/kg administered intraperitoneally (i.p.) did not significantly alter test latencies compared to the corresponding clock-time in saline-injected controls. Basal pain sensitivity and morphine-induced antinociceptive activity displayed significant circadian rhythms as assessed by the hot-plate response latencies, with higher values occurring during the nocturnal activity than during the daytime rest span. Acute administration of lithium, in a dose of 3 mmol/kg, 30 min prior to morphine dosing did not influence morphine-induced analgesia compared to all the clock-time test-matched morphine groups, except the 9 HALO (Hours After Lights On) one. There was a prominent potentiation of the morphine-induced antinociception at this biological time during combined drug treatment. The latter finding demonstrates that administration-time-dependent differences in drug-drug interactions need to be considered in both experimental designs and clinical settings.
authors.affiliation: Department of Medical Pharmacology, Faculty of Medicine, Gazi University, Besevler, Ankara, Turkey.
authors.forename: Elif Hilal
authors.initials: EH
authors.lastname: Karakucuk
authors.forename: Tarkan
authors.initials: T
authors.lastname: Yamanoglu
authors.forename: Ozlem
authors.initials: O
authors.lastname: Demirel
authors.forename: Nalan
authors.initials: N
authors.lastname: Bora
authors.forename: Hakan
authors.initials: H
authors.lastname: Zengil
mesh_terms: D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D008094:Lithium / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage*; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D010147:Pain Measurement
chemical_list: D000700:Analgesics; D009020:Morphine; D008094:Lithium