الفهرس 
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Abstract
There is a growing evidence that increased neurogenesis and brain-derived neurotrophic factor (BDNF) can be relevant to mood disorders. The modulation of neurogenesis and BDNF biosynthesis following prolonged antidepressant treatment may contribute to neuroplastic changes required for behavioural response.
The objective of this study is to assess the behavioural and neurogenic effects of duloxetine on BDNF in the rat brain. Duloxetine was administrated in doses 10, 20 and 27 mg/kg/day. After 21 days, all rats were subjected to behavioural tests namely forced swimming test (FST) and open field test (OFT). Measurement of serum corticosterone level, brain derived neurotropic factor concentration in the prefrontal cortex and the hippocampus as well as histological study was carried out. The results showed that duloxetine (10, 20 and 27 mg/kg/day) produced a statistically significant (p<0.0001) reduction in the serum corticosterone concentration. Duloxetine in doses of 20 and 27 mg/kg/day produced a statistically significant (p< 0.001) elevation of the BDNF concentration in the prefrontal cortex of the stressed rats while the elevation was statistically insignificant (p>0.05) with duloxetine in a dose of 10 mg/kg/day. Duloxetine in the three doses (10, 20 and 27 mg/kg/day) caused a statistically significant (p<0.05) elevationof BDNF concentration in the hippocampus of the stressed rats. Moreover, duloxetine treated rats improved the stress-induced cellular changes. It also reversed the stress induced behavioural changes. Duloxetine induced a statistically significant reduction in the immobility time (p< 0.001), a statistically significant increase in swimming (p< 0.001) and climbing time (p< 0.001) in the FST. It also showed a statistically significant decrease in the frequency of rearing (p< 0.01) and the number of total crossed squares (p< 0.05) in the OFT in the chronically stressed Wistar rats. Moreover, chronic duloxetine treatment showed a statistically significant positive correlation between the BDNF level in the PFC and the climbing time (r²=0.474, p= 0.009).The BDNF level in the PFC and swimming time showed statistically significant negative correlation (r²= -0.445, p= 0.016).
In conclusion, chronic duloxetine administration showed possible neurogenic effects on the rat prefrontal cortex and the hippocampus. This finding reflects an improved ability to cope under stressful conditions.