Investigation of effects of melatonin and fluoxetine combination on the immobilization stress model in mice

Exposure to stress triggers a lot of physiological and psychological illnesses. Studies show that the base for such effects of stress is related to hypothalamic-pituitary-adrenal (HPA) axis. Following desensitization to stress, HPA system is repressed and psychiatric diseases occur as a result. Many studies support that psychiatric disorders caused by stress respond to anti-depressant therapy. Widely and safely used in depression treatment, fluoxetine is known to have anti-depressant, anxiolytic and anti-oxidant effects. Melatonine, on the other hand, is thought to have anti-depressant effects and is known to be beneficial against oxidative damage triggered by stress. In our study, therapeutical effects of fluoxetine-melatonine combination on pathways induced by stress in rats have been researched with the immobilization stress model designed for the experiment. With this aim, male rats have been put into 8 groups; 1st group: control (1 ml of sterile saline intraperitoneal (i.p.) once a day for 7 days), 2nd group: immobilization stress group (IM) (1 ml of sterile saline (i.p.) once a day for 7 days), 3rd group: (IM) + Melatonine (Mel) (10 mg/kg (i.p.) once a day for 7 days), 4th group:(IM) + fluoxetin (Flu) (20 mg/kg (i.p.) once a day for 7 days), 5th group: IM + Mel (10 mg/kg (i.p.) once a day for 7 days) + Flu (20 mg/kg (i.p.) once a day for 7 days), 6th group: Mel (10 mg/kg (i.p.) once a day for 7 days), 7th group: Flu (20 mg/kg (i.p.) once a day for 7 days), 8th group: Mel (10 mg/kg (i.p.) once a day for 7 days) + Flu (20 mg/kg (i.p.) once a day for 7 days). After the seventh day, for each group, pain and weight controls were made, and changes in locomotor activity and anxiety by using controlled open field test, depression by using forced swimming test, anxiety by using elevated plus maze test and cognitive memory by using passive avoidance test were measured. Subjects were sacrificed by decapitation under ether anesthesia and their brain tissues isolated to be preserved at -80 degrees and for the assessment of oxidative damage, MDA levels were measured. As a result of the experiment, there was a statistically significant decrease in the weight of the IM subjects (p<0.05) as well as İM, İM+Mel, İM+Mel+Flu, Mel and Mel+Flu groups (p<0.05). According to the results of passive avoidance test, there was a statistically significant increase in the learning index of the IM group compared to the control group (p<0.01), and the learning index of IM+Mel and IM+Mel+Flu significantly decreased compared to the IM group (p<0.05). The results of the forced swimming test show inactivity increased and activity decreased in the IM group compared to the control group (p<0.05). In addition, activity in all the other groups showed significant increase compared to the IM group (p<0.01). According to the open field test, time spent in the periphery increased and the time spent in the center significantly decreased in the IM group in comparison to the control group (p<0.01). Compared with the IM group, there was a significant decrease in time spent in the periphery and a significant increase in time spent in the center by the other groups (p<0.01). In the elevated plus maze test, no statistically signifcant data was obtained (p>0.05). According to the MDA measurement, MDA in IM group significantly increasedcompared to the control group (p<0.01) and MDA in all the other groups decreased significantly compared to the IM group (p<0.05). In conclusion, stress was created successfully in the subjects by the use of immobilization and melatonine was shown to be at least as effective as fluoxetine in stress treatment but using a combination of these does not make a significant difference compared to using them separately.