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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
vii
possesses antidepressant activity, it also attenuated anhedonia, reversed body weight loss and
produced antipyretic effect induced by BCG induced depressive like behaviour.
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
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