Hippocampus is a region of the brain that is famous for its role in memory. However recently it has been given great importance for a region that regulates emotion and anxiety. Alternation of anxiety level has been observed in drug abusers as a comorbid disorder. The aim of this study is to show that morphine by altering oxidative stress in the hippocampus causes anxiety level alternation. In this study 32 male Sprague-Dawley rats divided into four groups: Control, N-acetyl-cysteine-treated, morphine-treated and N-acetyl-cysteine + morphine-treated. After 14 days of morphine administration (5 mg/kg/rat/i.p.) and N-acetyl-cysteine administration (100 mg/kg/rat/i.p.), Anxiety was assessed with Elevated Plus Maze (EPM) after 14 days in all groups. Then rats were euthanized and the hippocampus was removed for assessing oxidative stress for malondialdehyde (MDA), glutathione and nitrite/nitrate. Our data showed that oxidative stress was disturbed in the hippocampus in morphine-treated rats. Malondialdehyde (MDA) increased and glutathione and nitrite/nitrate were reduced in morphine-treated rats compared to control and N-acetyl-cysteine-treated rats. N-Acetylcysteine treatment improved oxidative stress (OS) markers and anxiety. The anxiety that was assessed with Elevated Plus Maze, morphine-treated rats showed less anxiety level compared to N-acetyl-cysteine -treated and control rats. Morphine reduced the anxiety level. The reduction of anxiety level was associated with oxidative stress imbalance in the hippocampus. Thus, hippocampus can alter anxiety level.

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