Abstract

Dr Merlin N. J. and Anusree S.*

ABSTRACT

Objectives: Major depression is a heterogeneous disorder it could not be fully controlled by a drug possessing one discrete mechanism of action so multi-modal treatment concepts are attracting attention. Nicotinic receptor antagonist had role in the treatment of depression. Therefore, this study was carried out to investigate the possibility of synergistic potential of dextromethorphan which is a nicotinic receptor antagonist with antidepressants for the treatment of depression. Also the effect of this combination on pain is tested in this study. Methods and Materials: Antidepressants such as duloxetine and venlafaxine at their median effective dose that is 30mg/kg, 8mg/kg i.p. respectively, were evaluated in combination with dextromethorphan 30mg/kg intraperitoneally for the synergistic potential for ameliorating depression in Swiss albino mice. Behavioural studies are carried out using forced swim test and tail suspension test. This was followed by the locomotor activity. The effect of these drugs on pain was checked by Eddy’s hot plate and tail immersion methods. The seratonin expression in brain was studied by RT-PCR method. Results: Behavioral studies indicated that antidepressant venlafaxine and duloxetine with dextromethorphan resulted in significant reduction in immobility time compared to the vehicle control in FST and TST, respectively. All the data were evaluated using the one-way analysis of variance followed by individual comparisons using Tukey's post-hoc test. Locomotor activity studies demonstrated no significant increase in general locomotion after co-administration of the compounds which shows that the reduction in duration of immobility with these drugs was due to antidepressant effect. RT-PCR shows more receptor expression in combination group. Conclusion: The present results suggest the concoction of dextromethorphan with venlafaxine and duloxetine for enhanced synergistic antidepressive effects with the reduction of dose.