| Summary: | Abstract Objective The present objective is to evaluate the antidepressant activity of caffeine. Material and methods Three groups of rats were used; control, reserpine-induced rat model of depression, and rat model of depression treated daily with caffeine. At the end of the experiment, the motor activity of rats was measured using open field test. On the next day, the animals of the three groups were sacrificed to measure levels of serotonin, norepinephrine, and dopamine in the cortex and hippocampus by spectrofluorometer. In addition, the levels of lipid peroxidation (MDA), nitric oxide (NO), and reduced glutathione (GSH) together with the activities of acetylcholinesterase (AchE) and Na+, K+, ATPase were measured in the two studied brain regions by spectrophotometer. Results In the rat model of depression, the animals showed a significant decrease in motor activity. This was associated with significant decreases in serotonin, norepinephrine, and dopamine in the cortex and hippocampus. However, significant increases in the activities of AchE and Na+, K+, ATPase, and the levels of MDA and NO were recorded in both areas of rat model of depression while GSH showed a significant decrease in the hippocampus. Caffeine failed to restore the decrease in motor activity. Caffeine treatment ameliorated the changes in cortical and hippocampal norepinephrine and dopamine and hippocampal serotonin. In addition, it restored MDA and GSH levels. However, it failed to prevent the increased AchE and Na+, K+, ATPase activities, and NO levels. Conclusions The present findings indicate that caffeine has a partial antidepressant effect mediated by its antioxidant activity and enhancement of monoamine levels.
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