الفهرس 
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Abstract
In the present study, the antidepressant effect of EGCG 25 and 50mg/kg on induction of depression was investigated. where imipramine was used as standard antidepressant agent. Depression was induced by intraperitoneal injection of clonidine to male albino rats at a dose 0.8mg/kg once daily for 7 consecutive days.
I-Three experiments of behavioral assessments with different degrees of stressfulness were selected to formulate an integrative testing battery. The chosen battery of tests allow to measure the most behavioral responses to the mentioned drugs.
This battery included the following experiments which were performed according to certain order depending on their level of stressfulness:
A. Open field test (mild stressful condition), in which latency time, ambulation frequency, defecation and rearing frequency were measured.
B. Forced swimming test: (hopelessness and despair behavior), in which immobility, swimming and climbing scores were measured.
C. Foot shock-induced aggression (model of defensive aggression rat vs rat), in which Latency to fight, jumping frequency and rearing frequency were measured.
II- Brains of rats not exposed to electricity were removed to determine monoamine levels using HPLC, for histopathological examination and for immunohistochemical detection of an inflammatory marker COX-2.The main findings of the present study can be summarized as follows:
A. Open Field Test:
1- Clonidine increased latency time while it decreased ambulation, rearing frequencies and defecation.
2- Imipramine did not affect ambulation or rearing frequencies but it affected latency time and defecation in depressed rats.
3- EGCG 25 mg/kg did not affect ambulation or rearing frequencies while 50mg/kg affected ambulation and rearing frequencies, But both doses decrease latency time and increase defecation in depressed rats.
4- EGCG 25 and 50mg/kg did not affect ambulation or rearing frequencies but decreased latency time and only 50mg/kg increased defecation when compared to depressed rats treated with imipramine.
5- EGCG 25 and 50mg/kg did not affect ambulation, rearing frequencies, latency time and defecation in normal control rats.
B. Forced Swimming Test:
1- Clonidine increased immobility score while it decreased swimming score with no effect on climbing score.
2- Imipramine decreased immobility score while it increased swimming score and climbing score in depressed rats.
3- EGCG 25 and 50mg/kg decreased immobility score while it increased swimming score and climbing score in depressed rats.
4- EGCG 25mg/kg did not alter immobility score, swimming score and decreased climbing score compared to depressed rats treated with imipramine while 50mglkg decreased immobility score while it increase swimming score and did not alter climbing score.
5- EGCG 25 and 50mg/kg did not alter immobility score, swimming score and climbing score in normal rats.
C. Foot shock-induced Aggression Test:
1- Clonidine decreased latency to fight while it increased jumping frequency with no effect on rearing.
2- Imipramine did not affect latency to fight, jumping frequency and rearing frequency in depressed rats.
3- EGCG 25 mg/kg did not alter latency to fight, jumping frequency and rearing frequency in depressed rats while 50mg/kg increased latency to fight, decreased jumping frequency and did not alter rearing frequency in depressed rats.
4- EGCG 25 and 50mg/kg did not alter latency to fight and rearing frequency compared to depressed rats treated with imipramine while 50mg/kg decreased jumping frequency.
5- EGCG 25 and 50mg/kg did not alter latency to fight, rearing frequency and jumping frequency in normal rats.
II. Brain Neurotransmitters Evaluations:
1-Clonidine decreased dopamine, serotonin and norepinephrine content in rat brain with respect to control group.
2-Imipramine increased dopamine, serotonin and norepinephrine content in rat brain with respect to depressed group.3-EGCG 25 or 50mg/kg increased dopamine and serotonin content in rat brain while only 50mg/kg increased norepinephrine with respect to depressed group.
4- EGCG 25 and 50mg/kg did not alter dopamine and serotonin content in rat brain while only 25mg/kg decreased norepinephrine with respect to depressed group treated with imipramine.
5- EGCG 25 and 50mg/kg did not alter norepinephrine and serotonin content in rat brain but increased dopamine content in normal group.
III. Histopathological examination of the brain:
Depressed group treated with clonidine (0.8mg/kg) and both depressed group treated with imipramine (15mg/kg) and EGCG (25mg/kg) showed focal gliosis with neuronal degeneration were detected in the cerebral cortex associated with focal gliosis also in the striatum of the cerebrum. The hippocampus showed neuronal degeneration associated with focal haemorrhage in the adjacent area of cerebrum. Haemorrhage was also noticed surrounding cerebellum. There was haemorrhage in the meninges covering the medulla oblongata. Depressed group treated with EGCG (50mg/kg) showed focal gliosis in the cerebral cortex.
IV. Immunohistochemical detection of Cox-2 in prefrontal cortex and hippocampus of the brain:
Depressed group treated with clonidine had increased COX-2 significantly than control group. Treatment with EGCG (25 or 50mg/kg) significantly decreased COX-2 expression than depressed-like group in the prefrontal cortex while only EGCG (50mg/kg) caused significant decrease in COX-2 expression in the hippocampus.Depending on the results of the present study it could be concluded that:
1. Clonidine resulted in a general reduction in locomotor and exploratory activity.
2. Clonidine induced depression associated with increase in aggressive behavior.
3. Imipramine at the selected dose did not change aggressive behavior induced by clonidine.
4. EGCG significantly reduced immobility in the FST but did not alter locomotor activity in the open field test at low dose, suggesting that GTP has antidepressant-like effects, and this action did not induce nonspecific motor changes.
5. Treatment with EGCG in a dose of 25 and 50mg/kg to depressed rats may show antidepressant action through affecting neurotransmitter systems as it significantly increased brain neurotransmitters.
6. EGCG has a promising antidepressant-like effect through its anti-inflammatory activity, as it decreased COX-2 expression.
7. EGCG (50mg/Kg) may reduce aggressive behavior in depressed rats.
8. Finally, it could be concluded that EGCG may has a promising antidepressant-like effect through its effect on neurotransmitters level and anti-inflammatory activity, where it managed to increase curiosity, self-interest, the will to live, increased swimming in FST, decreased COX-2 expression and all those effects are dose related.