Effect of Duloxetine Pretreatment on 5-HTP and Dexfenfluramine Induced Behaviours in Albino Rats

Abstract

Activation of central brain serotonergic receptors viz 5-HT1A and 5-HT2A by serotonin (5-HT) induces the 5-HT behavioural syndrome in rats. 5-HTP and dexfenfluramine produce 5-HT mediated behaviours. We have carried out the experiment with the aim to study the effect of duloxetine pretreatment on 5-hydroxytryptophan and dexfenfluramine induced behaviours in albino rats. Pre-treatment with 20 mg/kg duloxetine, a SNRI was found to potentiate 75 mg/kg 5-HTP mediated behavioural syndrome. However, 5, 10 and 20 mg/kg duloxetine had decreased the intensity of the behavioral syndrome produced by 10 mg/kg dexfenfluramine significantly. Duloxetine at 5, 10 and 20 mg/kg had produced inhibition of serotonin transporter (SERT) and inhibited dexfenfluramine uptake which had significantly antagonised its behavioural syndrome. Duloxetine at 5 and 10 mg/kg did not affect 5-HTP induced behavioral syndrome significantly where as 20 mg/kg duloxetine did significantly potentiate 5-HTP induced behavioral syndrome. This indicates 20 mg/kg dose of duloxetine blocks neuronal reuptake of 5-HT by blocking SERT and effectively increase its concentration to greater level in the synaptic gap which causes synergistic stimulation of the central postsynaptic 5-HT1A and 5-HT2A receptors and potentiation of 5-HTP behavioral syndrome.