The evaluation of the effects of paroxetine and venlafaxine on the tolerance induced by morphine on hot plate in mice

As a result of the chronic morphine administration, tolerance can develop to analgesic effect of morphine. The mechanism of tolerance induced by opioids could not be completely elucidated. Serotonin and noradrenaline play a major role in pain modulation. The studies have shown that norepinephrine level increases during the antinociceptive activity. Morphine administration caused an increase in serotonin turnover. In our study, 5-10-20 mg/kg doses of paroxetine and venlafaxine were evaluated for their effect on morphine tolerance in mice. As to be equal to the number of male and female, six study groups which are selected randomly from KTU Faculty of Medicine and Surgery Research Center Laboratory and using 96 mice in 25-50 g weight were formed. Physiological saline by oral gavage was administrated to control group and morphine (10 mg/kg/day, s.c.) was administrated to morphine group which was the group formed to evaluate morphine tolerance. Each of two experimental groups was divided into three sub-groups and 5-10-20 mg/kg paroxetine and venlaflaxin was administrated solely to each subgroup. Each of two remaining groups was divided into three sub-groups and 5-10-20 mg/kg paroxetine and 5-10-20 mg/kg venlaflaxin was administrated to each subgroup by oral gavage. Meanwhile; morphine (10 mg/kg, s.c) was administered to every mice in these two groups. Antinociceptif effect was evaluated on test animals which were drugs administered for eight days by taking the measurement of pre and post treatment. In conclusion, analgesic effect has been reduced significantly in morphine-tolerant group (p<0,05). Paroxetine and venlafaxine showed significant antinociceptive effects. Statistically significant reduction on the analgesic effect has not been shown on group of paroxetine+morphine and velafaxine+morphine. When the last measurements of the groups given drug combination and given solely morphine were compared that statistical differences were observed which depend on administered dose and drug.