Temporal variation in drug interaction between lithium and morphine-induced analgesia

Karakucuk E. H., Yamanoglu T., Demirel O., Bora N., Zengil H.

CHRONOBIOLOGY INTERNATIONAL, vol.23, no.3, pp.675-682, 2006 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 23 Issue: 3
  • Publication Date: 2006
  • Doi Number: 10.1080/07420520600650745
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.675-682
  • Gazi University Affiliated: No


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.