Bipolar disorder (BD)is a severe and chronic psychiatric disorder, characterized by recurrent mood episodes of depression and mania. Some studies have indicated that there are ERK and JNK pathways alterations in the brain from bipolar patients. The animal model of mania induced by dextroamphetamine (d-AMPH)has been considered an excellent model to study intracellular alterations related to BD. The present study aimed to evaluate the effects of lithium (Li)and valproate (VPA)on the behavioral and ERK1/2/JNK1/2 signaling pathway in an animal model of mania induced by d-AMPH. Wistar rats were first given d-AMPH or saline (Sal)for 14 days, and then, between the 8th and 14th days, the rats were treated with Li, VPA, or Sal. The open-field test was used to evaluate the locomotion and exploration behaviors of rats. The levels of phosphorylated ERK1/2 and JNK1/2 were assessed in the hippocampus and frontal cortex of the rats. Li and VPA reversed the increased of locomotion and exploration induced by d-AMPH. The treatment with VPA or AMPH per se decreased the levels of pERK1 in the hippocampus. The treatment with VPA in the animals submitted to the administration of d-AMPH decreased the levels of ERK1, JNK-1, and JNK-2 phosphorylated in the hippocampus of the animals. The treatment with Li decreased the JNK-1 phosphorylated in the hippocampus of the animals submitted to the animal model of mania induced by d-AMPH. Although the association of VPA plus amphetamine alters some proteins involved in the JNK pathway in the hippocampus, these alterations were very random and seemed that were not related to the d-AMPH-induced manic-like behavior. These results suggest that the manic-like effects induced by d-AMPH and the antimanic effects of mood stabilizers, Li and VPA, are not related to the alteration on ERK1/2 and JNK1/2 pathways.
Valvassori, S. S., Gava, F. F., Dal-Pont, G. C., Simões, H. L., Damiani-Neves, M., Andersen, M. L., … Quevedo, J. (2019). Effects of lithium and valproate on ERK/JNK signaling pathway in an animal model of mania induced by amphetamine. Heliyon, 5(5). https://doi.org/10.1016/j.heliyon.2019.e01541