IS THE MODULATION EFFECT OF MIDAZOLAM ON MORPHINE INDUCED ANTINOCICEPTION TIME DEPENDENT?

Aim: The aim of this study was to investigate the effects of midazolam, morphine and midazolam-morphine on nociception. Benzodiazepines are known to influence opioid analgesia, and variations can be expected in the interaction between benzodiazepines and opioids at different times of the day. Method: The effects of midazolam, morphine, and midazolam-morphine combination on nociception were evaluated with tail flick test in mice, with together the time-dependent changes. Midazolam has not any antinociceptive effect and it inhibited in a fashion dose-dependent the antinociceptive effect of morphine. Results: Control group injected with saline displayed a significant diurnal rhythmicity in the tail flick test significantly. Saline control group’s response latency at light hour (at 16.00 h, P < 0.05) was shorter than that at late dark hour (at 04.00 h) and early morning hour (at 08.00 h). Morphine injected animals had shorter response latencies in light hours (at 12.00 and 16.00 h, P < 0.01) than at late dark hour (at 04.00 h) and early morning hour (at 08.00 h). When midazolam was used in combination with morphine, the tail flick response latencies became significant shorter clearly at every experiment times (P < 0.001), however this inhibition was slightly lower at 04.00 h than the other hours. Conclusion: Our results indicate that midazolam antagonism on morphine antinociception have not diurnal rhythmicity, however it may only slight decreased at late dark hours of day