Depression is a chronic and recurrent psychiatric disorder affecting mental and physicalrnhealth. Traditional medicines have been used for decades in the treatment of depression rndue to resistance development, side effects, inadequate accessibility and affordability ofrnmodern antidepressant drugs. The root bark of Carissa spinarum Linn. (Apocynaceae), rnwhich is used traditionally for depression is reported to possess antidepressant- like activit yrnin rodent models of depression. In the current study, different fractions of the root barkrnobtained using solvents of different polarities were investigated using a host of models, rnincluding tail suspension test (TST), forced swim test (FST), muricidal behavioral test, andrnopen field test (OFT). Moreover, markers for depression and phytoconstituents were rndetermined, and preliminary mechanistic studies using different drugs were alsornconducted.rnFive groups of animals of either sex each having 6 animals per group were randomly rnassigned for every model and each solvent fraction (Ethyl acetate, n-butanol, and aqueous).rnGroup I, served as a negative control group and received a vehicle (2% Tween 80), group rnII served as a positive control and received the standard drug Imipramine (30 mg/kg), grouprnIII-V received increasing doses of the solvent fractions 50, 100 and 200 mg/kg,rnrespectively. Ethyl acetate (CSE) and n-butanol (CSB) fractions significantly (p