Prevention of morphine dependence and tolerance by Nepeta menthoides was accompanied by attenuation of Nitric oxide overproduction in male mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Repeated administration of morphine for chronic pain leads to dependence and tolerance that limits clinical usage. Nepeta menthoides is commonly known as Iranian Ustukhuddoos and are administered in traditional medicine for gastrodynia, bone pain, blood depurative and restlessness.

AIMS OF STUDY: To investigate the effects of Nepeta menthoides on expression and acquisition of morphine dependence and tolerance in mice with regard to oxidative stress.

MATERIALS AND METHODS: Morphine dependence in mice was developed by administration of gradually increasing doses of morphine twice daily for 7 consecutive days. In experimental groups, administration of Nepeta menthoides (200 and 400mg/kg), methadone and their combination were performed 60min prior to each morphine injection (for acquisition) or the last injection of morphine on test day (for expression). Morphine tolerance was measured by the tail-immersion test before and after the administration of a single dose of morphine (100mg/kg; i.p.) on the test day (8th day). Morphine dependence was also evaluated by counting the number of jumps after the injection of naloxone (5mg/kg; i.p.).

RESULTS: Nepeta menthoides, similar to methadone, significantly prevented the development (but not the expression) of morphine dependence, tolerance, and potentiated morphine antinociception and also reduced (23.23±1.15) Nitric oxide (NO) overproduction (35.23±3.36) (in compared with naloxone group (6.3±0.52)). However, single and repeated application of the extract could not change high single-dose morphine analgesia.

CONCLUSION: It appears that Nepeta menthoides and methadone prevented morphine dependence and tolerance, partly through inhibition of the NO overproduction.