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

Authors

Abstract

 Background and
Objective:
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.    Materials and Methods: 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.   Results: 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.   Conclusion: Our results showed that probably methadone and
valproate combination treatment could reduce tolerance and dependence more than single valproate or methadone
treatments. 

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