Razi Journal of Medical Sciences

Background: Today opioids are used to control and relieve acute and chronic pain. However, the incidence of both tolerance and dependence phenomena are the two major problems in the people who take these drugs. So, in this study the combination effect of haloperidol and methadone on the acquisition and expression of morphine dependence and tolerance have been examined.

Methods: In this experimental study ninety-eight NMRI male mice were randomly divided into acquisition and expression groups. Each group was divided into seven sub-groups: control, sham (saline), methadone, haloperidol, haloperidol + methadone, methadone + haloperidol ratio of 2 to 1 and methadone + haloperidol ratio of 1 to 2. All groups were addicted with gradually increasing doses of morphine for 7 consecutive days. All drugs, in the acquisition group were injected 30 minutes before morphine injection for 7 days and in the expression group 30 minutes before morphine injection on the 8th day (test day). Morphine tolerance was measured by tail immersion test for 30 minutes before and after administration of morphine on the test day. To assess the dependence, mice were administered with naloxone and then withdrawal behaviors were observed for 30 minutes. Then data were analyzed using one-way ANOVA by sigma stat software.

Results: Chronic morphine injections induced tolerance and dependence in mice. Percentage of Maximal Possible Effect (MPE) as a tolerance index was significantly increased in acquisition and expression groups which received drugs combination methadone 1 + haloperidol 2 as compared to control groups. About the dependence, the marked decrease was shown in withdrawal behaviors in the combination therapy groups.

Conclusions: However, our results have shown that probably methadone and haloperidol combination treatment, especially in the ratio of 1 to 2 could reduce tolerance and dependence more than single drug treatment animal groups.