Methadone and valproate combination effect on acquisition and expression of morphine dependence and tolerance in male mice

According to the problem of dependence and tolerance in addicted patients، the inefficiency of existing treatments and the new sciences recommendation of drug combination therapy for diseases in modern pharmacology، the present study examined the effects of methadone and valproate combination on morphine tolerance and dependence. Ninety-eight male mice were divided into following groups: saline، morphine، methadone، valproate، three groups of valproate+methadone، i. e 1 to 1، 2 to 1 and 1 to 2 ratio. Except saline group، other groups received escalating dose of morphine for 8 consecutive days. In acquisition group، drugs were injected for 30 minutes before morphine administration. But in expression group، the drugs were used only at 8th day (test day) as mentioned method. Morphine tolerance was measured by tail immersion test and for the dependence، naloxone-induced withdrawal signs assessment was applied. Jumping behavior as a main dependence signs in both acquisition and expression significantly reduced in methadone1+ valproate2 treatment groups. Also، acquisition and expression in tolerance evaluation significantly decreased in valproate and methadone1+valproate2 more than other groups. Our results showed that probably methadone and valproate combination treatment could reduce tolerance and dependence more than single valproate or methadone treatments.