Lithium modulates energy metabolism in the frontal cortex of rats treated with ketamine

Bipolar Disorder (BD) is a chronic and highly debilitating psychiatric illness formerly called manic depression. Mood-stabilizing agents such as lithium (Li) are the primary drugs used to treat BD. Assessing the effect of these mood stabilizers is essential to develop a novel animal model of mania. Thus, the present work aimed to evaluate the ketamine (Ket) effect on tricarboxylic acid enzymes and mitochondrial respiratory chain complexes activity in the frontal cortex of rats for consolidation of an animal model of mania induced by Ket. Wistar rats received Ket (25 mg/kg) or saline for 14 days. Between days 8 and 14, the rats were treated with Li (47.5 mg/kg, twice daily) or saline for 14 days. On the 15th day, animals received a single injection of Ket or saline. After 30 minutes of the last injection, the locomotor activity was assessed, and tricarboxylic acid and mitochondrial respiratory chain complexes enzyme activities were measured in the frontal cortex. The administration of Ket for 14 days in rats induced hyperlocomotion in the open field test, and Li was able to reverse this effect. Moreover, animals treated with Ket increased the tricarboxylic acid cycle and mitochondrial respiratory chain complexes enzyme activities in the frontal cortex. Lit was able to reverse these effects, but could not reduce the mitochondrial respiratory chain complexes IV activity. These findings support the idea that the administration of Ket might be a promising pharmacological animal model of mania, but there is a limitation in construct validity for energy metabolism.