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العنوان
Effect of Metformin on the Antidepressant Activity of Fluoxetine in Rats Fed High Fat Diet and Exposed to chronic Stress/
المؤلف
Khedr,Sara Adel Ahmed
هيئة الاعداد
باحث / ساره عادل احمد خضر
مشرف / هدي عبد الجليل سلام
مشرف / أحمد عبد السلام محمد المليجي
مشرف / سوسن ابو الفتوح السيد
مشرف / امنية على الخراشى
مشرف / منال لويس لوقا
تاريخ النشر
2016
عدد الصفحات
615
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
علم الأدوية (الطبية)
تاريخ الإجازة
1/1/2016
مكان الإجازة
جامعة عين شمس - كلية الطب - Pharmacology
الفهرس
Only 14 pages are availabe for public view

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Abstract

Background &Aim: Several hypothesis link high fat diet and depression, we aimed to study the effect of metformin (MET) on the antidepressant activity of fluoxetine (FLU) in non-high fat diet (HFD) and HFD fed rats exposed to chronic restrained stress (CRS).
Methods: Ten groups (n=12) of male Wister rats were used. Naïve rats (control, non-stressed, fed standard chow diet for 12 weeks), 4 stressed groups (exposed to CRS 4 hours daily in the last 6 weeks), fed standard chow for 12 weeks, [untreated, MET treated, FLU treated, MET and FLU treated groups]. HFD fed group for 12 weeks (control group), 4 stressed and HFD fed groups [untreated, MET treated, FLU treated, MET and FLU treated groups]. MET and FLU were given daily by oral gavage in a dose of 30mg/kg and 10mg/kg respectively in the last 4 weeks of 12 weeks total duration. Behavioral, biochemical, molecular and histopathological studies were performed.
Results: stressed non HFD fed group showed depressive like symptoms, disturbed glucose homeostasis and lipid profile, reduced adiponectin level and BDNF expression, while corticosterone and phosphorylated JNK were increased. All this was aggravated by HFD.
The treatment with metformin, fluoxetine and their combination produced significant improvement HDL, triglycerides, IR and serum corticosterone levels, behavioral tests, body weight, fasting insulin, LDL, total cholesterol, fasting glucose, adiponectin. There was also significant improvement in phosphorylated hippocampal JNK level as well as BDNF gene expression. H&E results show increase in number of viable cells in CA3 and decreased number of shrunken pyramidal cells in hippocampus.
However, the significant difference favors the combination of metformin and fluoxetine.