Acute effects of serotonergic antidepressants on tryptophan metabolism and corticosterone levels in rats

ABSTRACT

The aim of present study is to see the effects of antidepressants in relation to tryptophan metabolism and disposition and to know whether they share any common mechanism of action in this regard. These are the monoamine oxidase inhibitor [moclobemide], atypical tricyclic [tianeptine], selective serotonin reuptake inhibitors [SSRIs] namely sertraline and citalopram and an herbal St John's Wort [SJW]. Liver tryprophan pyrrolase activity, serum tryptophan, corticosterone and brain indoles were determined after drug administration in Albino Wistar rats at a dose of 10mg/kg. All five antidepressants inhibited tryptophan pyrrolase activity. Serum total tryptophan concentrations were increased by 19% and 33% by tianeptine and moclobemide respectively, however 34% decrease in total tryptophan was observed after SJW administration. Free tryptophan was increased by all the drugs being maximum [65% P<0.001] by sertraline and minimum [15%, P<0.05] by tianeptine. Corticosterone levels were significantly [P<0.01] decreased by 52 and 58 percent by citalopram and St John's Wort respectively. By contrast an increase by 16% was observed by tianeptine. It was also observed that all the drugs increase brain tryptophan by 21-61 percent but increases in 5-hydroxytryptamine [5-HT] were observed only by two drugs that is moclobemide and SJW, however in comparison increases were greater [68%] after SJW administration. 5-hydroxyindoleacetic acid [5HIAA] concentrations were increased by 45-64% by all other drugs except tianeptine and moclobemide. It is concluded that attenuation of peripheral tryptophan metabolism and elevation of brain tryptophan contributes to the mechanism of action of antidepressants of different classes and pharmacological profile tested