Study on the anti-depressant and anxiolytic activities of the methanolic leaf extract of mitragyna speciosa korth and its effect on the level of some brain biogenic amines

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Date
1998
Authors
Abushwereb, Hanan Saaddin
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Abstract
Mitragyna speciosa Korth (Family: Rubiaceae) locally known as "Daun Biak", has· been shown to have addictive properties and produce tolerance and dependence. The methanolic leaf extract of Mitragyna speciosa (MS) is known to contain several alkaloids including mitragynine which has an indole moiety. This moiety is also a feature of serotonin, which is an important central neurotransmitter. In view of the current strategy of designing antidepressants in the form of reuptake inhibitors (SSRis), ~selective serotonin this study has investigated whether the methanolic leaf extract of Mitragyna speciosa possesses antidepressant-like effect. Mitragyna speciosa has also been used as an opium substitute probably to alleviate anxiety by drug abusers when the drug itself is unavailable. Therefore, this study has also investigated if the methanolic leaf extract of Mi tragyna speciosa has such anxiolytic-like effect. In order to elucidate the possible mechanism of action of Mitragyna speciosa, the level of neurotransmitters have also been determined. The Porsolt antidepressants swim had test been method used for for screening the first objective. Female mice were forced to swim for 6 minutes into a glass cylinder (height 27cm and diameter 16.5cm) filled with 11cm water at 27°C. This was followed 24h later with a second swim session of 6 min. Drugs were administered (n=10) orally 1, 5 and 24h after the first swim session to record chronic effect. The oral administration of Mitragyna speciosa methanolic leaf extract at doses 100, 200, 400 mg/kg, significantly reduced the immobility time. The antidepressant-like effect of the Mi tragyna speciosa methanolic leaf extract was I' compared to that of imipramine. The locomotor activity of the methanolic leaf extract was measured to confirm that the reduction in immobility time was not due to the increase in locomotion. In addition, the plus-maze and open-field test of exploratory behaviour were used for measuring the anxiolytic-like effect of the extract. Chronic administration of the Mitragyna speciosa methanolic leaf extract 50, 100, 200 and 400 mg/kg, orally for 14 days on rats tested in the elevated plus-maze, 2 4 h after the last administration, was found to produce an anxiolytic-like effect on their exploratory behaviour at doses 100, 200 and 400 mg/kg. However, the effect of the methanolic leaf extract on the general locomotor activity were not found to be significantly changed. The effect of this methanolic leaf extract were compared to that of diazepam. At by the time of plus-maze testing and open the anxiolytic field, the like-effect levels of different monoamines in four brain areas named; the substantia nigra, the nucleus accumbens, the locus coeruleus, and the raphe nuclei were also assayed using high performance liquid chromatography coupled with electrochemical detector (HPLC-EC). The levels of serotonin were found to be significantly higher in substantia nigra in doses of 100 and 200 mg/kg of the methanolic leaf extract of Mitragyna speciosa, while the serotonin metabolite (5-hydroxyindoleacetic acid) was increased in raphe nuclei and nucleus accumbens at doses 100, 200 and 400 mg/kg of the Mitragyna speciosa methanolic leaf extract. An increase in noradrenaline levels in the four tested regions; the locus coeruleus, nucleus accumbens, substantia nigra and raphe nuclei was also observed in doses of 100, 200 and 400 mg/kg. The dopamine levels were increased in substantia nigra and accumbens in doses of 100, 200 and 400 mg/kg. The results of the present study suggest that the antidepressant- and anxiolytic-like effect - of the Mitragyna speciosa extract, is probably mediated mainly through the enhancement of central neurotransmitter levels.
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Anti-depressant , Methanolic leaf extract , Brain biogenic amines
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