Effects of the ethanolic extract of mitragyna speciosa leaves on morphine addiction in mice and rats

Abstract

Mitragyna speciosa Korth. (Rubiaceae) has been used for the treatments of pain, fever, cough, diarrhea, opioid-addiction in Thai traditional medicine for a long time and also for enhancing the labor work efficiency and tolerance under the hot sunshine atmosphere. Until now, there is no clear evidence of the rewarding effects of M. speciosa in animal models. The present study was aimed to determine the effects of the ethanolic extract of M. speciosa leaves (MS) on the locomotor activity, rewarding effect and morphine addiction in rodents. Three models including locomotor activity test, conditioned place preference test (CPP) and precipitated withdrawal with opioid antagonists were utilized in this study. The results showed that morphine (5 mg/kg i.p.) could induce significant CPP while all doses of MS (50, 100, 200 and 400 mg/kg p.o.) neither changed locomotor activity nor produced CPP. The morphine-induced CPP was suppressed by all doses of MS. In precipitated withdrawal models of acute and chronic MS treatments, all doses of MS did not show any significant withdrawal symptoms. In contrast, morphine exhibited significant withdrawal symptoms including jumping, straub tail, C-shaped tail, and wet dog shakes. Then the effects of pretreatment and post-treatment of MS on morphine withdrawal were evaluated. The results showed that both pretreatment and post-treatment with all doses of MS significantly attenuated jumping behavior precipitated by naloxone (p<0.05). In conclusions, MS did not have psychostimulating, sedative or rewarding effects and did not produce any significant precipitated withdrawal symptoms after acute or chronic uses. Furthermore, it could suppress morphine-induced CPP and morphine withdrawal symptoms. The results suggest that MS might be helpful in the treatment of morphine and other opioid addiction.