Prof. Engidawork, EphremSaif, Hana2022-05-182023-11-062022-05-182023-11-062022-03http://etd.aau.edu.et/handle/123456789/31685Depression is a chronic and recurrent psychiatric disorder affecting mental and physical health. Traditional medicines have been used for decades in the treatment of depression due to resistance development, side effects, inadequate accessibility and affordability of modern antidepressant drugs. The root bark of Carissa spinarum Linn. (Apocynaceae), which is used traditionally for depression is reported to possess antidepressant- like activit y in rodent models of depression. In the current study, different fractions of the root bark obtained using solvents of different polarities were investigated using a host of models, including tail suspension test (TST), forced swim test (FST), muricidal behavioral test, and open field test (OFT). Moreover, markers for depression and phytoconstituents were determined, and preliminary mechanistic studies using different drugs were also conducted. Five groups of animals of either sex each having 6 animals per group were randomly assigned for every model and each solvent fraction (Ethyl acetate, n-butanol, and aqueous). Group I, served as a negative control group and received a vehicle (2% Tween 80), group II served as a positive control and received the standard drug Imipramine (30 mg/kg), group III-V received increasing doses of the solvent fractions 50, 100 and 200 mg/kg, respectively. Ethyl acetate (CSE) and n-butanol (CSB) fractions significantly (p<0.001) reduced the duration of immobility in TST and FST, while the aqueous fraction (CSA) failed to show any appreciable antidepressant- like activity. No change in the locomotor activity using OFT was observed at all doses. From the two active fractions, the ethyl acetate fraction was the most effective and contributed to reducing the muricidal behavior in rats. Serum corticosterone level was reduced by both fractions and once again the ethyl acetate fraction was the most effective. Mechanistic studies revealed the involvement of multiple neurotransmission systems, including adrenergic, dopaminergic and choline r gic as well as the L-Arginine-NO-cGMP pathway in the antidepressant- like effect of the plant, hence only both the dopaminergic and the L-Arginine-NO-cGMP pathway were the predominant by which the ethyl acetate fraction might mediate its action. Phytochemica l analysis showed the presence of high content of alkaloids (0.17 mgATE/g and 0.07 mgATE/g), flavonoids (12.43 mgQE/g and 2.07 mgQE/g), and phenols (42.42 mgGAE/g and 29.8 mgGAE/g) for CSE and CSB, respectively. The findings collectively indicate that CSE and CSB are endowed with antidepressant- like activity due to the presence of phenols, flavonoids, and alkaloids, which are medium polar in nature.en-USDepression, Carissa spinarum Linn., Antidepressant-like activity, Solvent Fractions, Forced Swim Test, Tail Suspension Test, Muricidal Behavioral Test, Open Field Test, Serum Corticosterone Level, Pharmacological drugs.Thesis