ABSTRACT

The leaves ofZiziphus mauritiana have been reported to be used in the management of

depressive illnesses in traditional medicine. The antidepressant activity of the methanol leaf

extract of the plant was evaluated using tail suspension test (TST) and forced swim test (FST) at

the doses of 25, 50, 100, and 200 mg/kg.Imipramine (20mg/kg) was used as standard

antidepressant drug.The effect of the extract on recognition memory, motor coordination, and

exploration was evaluated using novel object recognition test (NORT), beam walking assay test

(BWAT) and open field test (OFT) respectively. In order to establish the involvement of

inflammatory system in the antidepressant activity of the extract using    Bacillus

Calmette-Guérin(BCG) induced depressive like behaviour modelthrough chronic activation of

the immune system in the chronic study, mice were inoculated with BCG (0.2 mg/kg, i.p) and

later treated with the graded doses of the extract for 21 days. Body weight was measured 4 days

before the inoculation and on daily based after, while the body temperature was recorded hourly.

Exploration, immobility time and sucrose consumption were all assessed using open field test,

tail suspension test and sucrose preference test respectively.Data wererepresented as± SEM and

analyzed using one-way (treatment) or two-way (treatment × time) analysis of variance

(ANOVA), followed by the Bonferroni post hoc test whereP< 0.05 was considered significant

.The results showed a statistical significant ( p < 0.001) decrease in duration of immobility,

significant (p < 0.001) increase in sucrose consumption,significant (p < 0.001) decrease in body

temperature,significant (p < 0.001) increase in body weight in the extract treated groups when

compared with the BCG + distilled water. The LD50 of the extract was >5000 mg/kg and

phytochemical screening revealed the presence of flavonoids, alkaloids, tannins, cardiac

glycoside, and saponins. It was concluded that the methanol leaf extract of Ziziphus mauritiana

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CHAPTER ONE

1.1 Introduction

Depression is a neuropsychiatric disorder affecting a huge percentage of the active population

especially in developed countries (Neto etal.,2011). Itis an affective state of negative mood and

low arousal that presents with depressed mood, loss of interest or pleasure, decreased energy,

feelings of guilt or low self-worth, disturbed sleep or appetite, and poor concentration. Moreover,

it often comes with symptoms of anxiety. These problems can become chronic or recurrent and

lead to substantial impairments in an individual ability to take care of his or her everyday

responsibilities. At its worst, depression can lead to suicide(WHO 2012). According to the current

text revision version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V),

depression constitutes an episode of major depressive disorder (MDD) if it is denoted by at least

five of nine symptoms: depressed mood, anhedonia, significant weight loss (or gain), or a

decrease (or increase) in appetite, insomnia (or hypersomnia), psychomotor retardation (or

agitation), fatigue or loss of energy, feelings of worthlessness or guilt, diminish ability to

concentrate; and recurrent thoughts of death (not just fear of dying), or suicidal thoughts or

actions (American Psychiatric Association, 2013). Additionally, the episode must last for at least

2weeks, and it must cause substantial distress or impairment in an important domain of

functioning. Finally, the episode must not be better accounted for by bereavement (which