ETHIOPIAN PHARMACEUTICAL JOURNAL Ethiop. Pharm. J. 30, 21-32 (2014) http://dx.doi.org/10.4314/epj.v30i1.3 Depression is an important global public health problem due to both its relatively high lifetime prevalence and being a leading cause of disability, workplace absenteeism, decreased productivity, and high suicide rates (WHO, 2007). A recent World Health Organization (WHO) report predicts that de- pression will be the leading cause of disabil- ity and premature death in the industrial world, and unipolar major depression to be the second largest cause of global disease problems in the world, only behind ischemic heart disease by the year 2020 (Kozisek et al., 2008). Until the late 1980s, depression was treated with electroconvulsive therapy and antidepressant drugs known as monoam- ine oxidase inhibitors (MAOIs) and tricyclic antidepressants but later on these are super- seded by agents like selective serotonin reup- take inhibitors (Licinio and Wong, 2005). Although treatment with these commer- cially available antidepressant drugs is effec- tive, a significant number of patients do not achieve continuous remission, despite inten- sive management. Moreover, only 60% of patients are responsive to currently available antidepressants. The unpredictable clinical response to antidepressant drugs, a need to administer up to 6-8 weeks to see the antide- pressant effect and high susceptibility to ad- verse effects are major clinical problems. Thus, new drugs are still needed to treat de- pression-related disorders (Schloss and Henn, 2004; Kwon et al., 2010). Prior to the application of synthetic anti- depressant drugs, many traditional medicines and empirical formula were successfully used to treat depression-like disorders. Plants of the genus Hypericum have traditionally been used as medicinal plants in various INTRODUCTION Screening of the Antidepressant-like Activity of Two Hypericum Species Found in Ethiopia 1 Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia The widespread use of Hypericum perforatum for the treatment of mild to moderate depression has prompted screening of the antidepressant-like effect of other species of the genus. The present study was designed to assess the antidepressant-like activity of the 80% methanol extract of Hypericum quartinianum and Hypericum revolutum in behavioral despair model. Eighty percent methanol extract of H. quartinianum and H. revolutum was investigated using learned helplessness models of depression such as tail suspension test (TST), forced swimming tests (FST) and avoidance tests. In addition, locomotor activity was investigated with open field test (OFT). Mice (for TST, avoidance test and OFT) and rats (for FST) were randomly assigned into different groups and treated with distilled water (control), imipramine 64 mg/kg (standard) and extract (200 mg/kg and 400 mg/kg). At 200 and 400 mg/kg, H. revolutum was effective in reducing immobility time in the TST (43.84%, p<0.01 and 49.08%, p<0.01, respectively) and FST (33.7%, p<0.05 and 38.4%, p<0.01, respectively). Similarly, H. quartinianum also showed anti-immobilty effect at 200 (30.67%, p<0.01) and 400 mg/kg (41.19%, p<0.01) in TST. However, only the larger dose produced significant anti-immobility effect in FST (35.3%, p<0.05). Moreover, both extracts at the doses used significantly decreased the escape failure (p<0.01) and increased the intertrial crossing (p<0.05 and p<0.01) during the resting periods in the avoidance task in a shuttle box. In OFT, the tested crude extracts did not significantly alter locomotor activity, suggesting that it is very unlikely that the observed antidepressant effects are false positives. These observations together provide evidence that the 80% methanolic extract of leaves of H. quartinianum and H. revolutum display antidepressant-like actions in established models of behavioral despair without affecting locomotion. Keywords: Hypericum quartinianum, Hypericum revolutum, depression, antidepressant-like activity Abebe Ejigu 1 and Ephrem Engidawork 1* * Correspondence: ephrem.engidawork@aau.edu.et ETHIOPIAN PHARMACEUTICAL JOURNAL Ethiop. Pharm. J. 30, 21-32 (2014) http://dx.doi.org/10.4314/epj.v30i1.3