Effect of various classes of antidepressants in behavioral paradigms of despair

Abstract

The forced swim test (FST) and tail suspension test (TST) are widely used as animal models for screening potential antidepressants. Immobility or despair behavior produced in both FST and TST are taken as paradigm of depression and antidepressant drugs reduce the immobility period. Recent studies have suggested dissimilar hemodynamic, behavioral, physiological and pharmacological variations in these two models. Also, studies have proposed the significance of strain in these models of despair in an attempt to replicate results from one laboratory to another. The present study was undertaken to compare the antidepressant action of four major classes of antidepressants namely tricyclics (imipramine), selective serotonin reuptake inhibitor (fluoxetine), dual reuptake inhibitor of serotonin and norepinephrine (venlafaxine) and atypical antidepressants (mianserin and trazodone) using male laca mice in order to validate the two test procedures. Total immobility period was recorded during the period of 6 min in both the tests and the results were expressed as percentage decrease in immobility period with respect to vehicle control. Chlorpromazine (4 mg/kg, i.p.) or pentobarbitone (20 mg/kg, i.p.) were used as negative control. Imipramine (2, 5, 10 and 20 mg/kg), fluoxetine (5, 10, 20 and 40 mg/kg), or venlafaxine (2, 4, 8 and 16 mg/kg) dose dependently decreased the immobility period in mice. ED 50 values of imipramine, fluoxetine, and venlafaxine in FST and TST were found to be 9.2 and 10 mg/kg i.p, 18 and 20 mg/kg, i.p., and 8.5 and 12 mg/kg, i.p respectively. The relative potency of standard drugs in both FST and TST is imipramine = venlafaxine > fluoxetine. Mianserin (16 and 32 mg/kg., i.p.) or trazodone (1 and 2 mg/kg., i.p.) were ineffective to reduce the immobility period in both the tests showing the atypical nature of these antidepressants. Chlorpromazine or pentobarbitone was ineffective in reversing the immobility period thus validating the models for testing antidepressants. The present study further validated that both the test procedures are equi-sensitive to antidepressant drugs of different class in the strain of animals used.