[Effect of methadone and valproate combination on morphine withdrawal-induced anxiety and depression in male mice]

ABSTRACT

Anxiety and depression are experienced following addicted patients durg withdrawal. This study was done to determine the effect of methadone and valproate combination on morphine withdrawal-induced anxiety and depression in male mice. In this experimental study, ninety-eight male mice were allocated into acute and chronic categories. Animals in acute chronic categories allocated into seven groups including saline, morphine, methadone [10 mg/kg/bw], valproate [150 mg/kg/bw], three groups of valproate+methadone, in of ratio 11, 21 and 12. Animals were received escalating dose of morphine for 8 consecutive days except saline group. In chronic group, drugs were injected for 30 minutes before morphine administration, while in acute group; the drugs were used only at day 8. Anxiety and depression due to naloxone injection [5 mg/kg/bw]was investigated by elevated plus-maze, tail-suspension and open field tests. In the chronic group, valproate + methadone [21] combination therapy showed a significant increase in the percentage of open arm entries [53.86 +/- 1.9] and percentage of time spent in the open arm [58.58 +/- 4.15] compared to the morphine group, with a percentage of entering [28.12 +/- 2.03] and percentage of time [17.88 +/- 1.77] [P<0.05]. In open field test, the ratio of the number to the duration of time spent in the central square, in the combination therapy groups of methadone+valproate[27 +/- 2], valproate+methadone [12] and valproate+methadone [21] were significantly increased in compare to the morphine group [P<0.05]. In tail-suspension test, duration of immobility as an indicator of depression, in the treatment group of valproate+methadone [21] was significantly reduced [P<0.05]. Valproate and methadone combination therapy particularly in ratio of 21 can reduce morphine withdrawal-induced anxiety and depression in animal model