Omega-3 fatty acids combined with aripiprazole and lithium modulates activity of mitochondrial enzymes and acetylcholinesterase in methylphenidate-induced animal model of mania

• This study was investigated the changes in Krebs cycle enzymes in an animal model of mania.
• The activities of Krebs cycle enzymes and AChE were measured in the brain.
• MPD inhibited the activities of Krebs cycle enzymes and AChE in brain.
• Lithium, aripiprazole, and omega-3 fatty acids significantly reversed MPD induced disparities of mitochondrial enzyme and acetylcholinesterase activity.

Many studies have shown the alterations of mitochondrial complexes in bipolar disorder (BD) patients. However, changes in the Krebs cycle enzymes have been little studied.The animal model of mania induced by psychostimulants like amphetamine and methylphenidate (MPD) has been widely used to study the manic phase of bipolar disorder. The aim of the present study is to assess the changes in the activity of Krebs cycle enzymes and acetylcholinesterase (AChE) in an animal model of mania induced by MPD. wiss albino mice were first administered intraperitonially with MPD (5 mg/kg) or saline for 14 days, upon changes in the behavioral activity, animals were treated with lithium (50 mg/kg), omega-3 fatty acids (1.5 ml/kg) given orally and aripiprazole administered intraperitonially (1.5 mg/kg) from 8th day onwards. Activity of Krebs cycle enzymes and AChE were measured in brain. Administration of MPD inhibited the activity of Krebs cycle enzymes and AChE in brain. Treatment with lithium, aripiprazole and omega-3 fatty acids significantly reversed MPD induced mitochondrial dysfunction and AChE activity. This finding suggest that lithium, aripiprazole and omega-3 fatty acids exert protective effect against MPD induced impairment of Krebs cycle enzymes in brain of mice; further supporting the hypothesis that mitochondrial dysfunction may be associated with the pathophysiology of BD.

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