Fos-like immunoreactivity in rat dorsal raphe nuclei induced by alkaloid extract of Mitragyna speciosa

Mitragyna speciosa (MS) has been traditionally used for medicinal purposes especially in southern Thailand. Previously, an alkaloid extract of this plant was demonstrated to mediate antinociception, partly, through the descending serotonergic system. The present study investigated the stimulatory effect of the MS extract on the dorsal raphe nucleus and its antidepressant-like activity. The MS extract containing approximately 60% mitragynine as a major indole alkaloid was used to treat the animals. The stimulatory effect of the MS extract was determined by detecting the expression of the immediate early gene, cfos, in the dorsal raphe nucleus of male Wistar rats. The immunohistochemistry was used to detect Fos protein, the protein product of cfos gene. The present data show that a significant increase in Fos expression was observed following long-term administration of the MS extract (40 mg/kg) for 60 consecutive days. In addition, the antidepressant-like activity of the MS extract was determined by using the forced swimming test (FST) in male mice. The results show that a single injection (either 60 or 90 mg/kg doses) significantly decreased immobility time in the FST. These findings indicate that the MS extract has a stimulatory effect on the dorsal raphe nucleus and an antidepressant-like activity. Stimulation of this brain area has been known to cause antinociception. These findings suggest that the MS extract might produce antinociceptive and/or antidepressive actions partly through activation of the dorsal raphe nucleus. Moreover, the dorsal raphe nucleus may be one of site of MS action in the central nervous system.