Lithium and Tamoxifen Modulate Behavior and Protein Kinase C Activity in the Animal Model of Mania Induced by Ouabain.
Background
The intracerebroventricular injection of ouabain, a specific inhibitor of the Na+/K+-adenosine-triphosphatase (Na+/K+-ATPase) enzyme, induces hyperactivity in rats in a putative animal model of mania. Several evidences have suggested that the protein kinase C signaling pathway is involved in bipolar disorder. In addition, it is known that protein kinase C inhibitors, such as lithium and tamoxifen, are effective in treating acute mania.


Methods
In the present study, we investigated the effects of lithium and tamoxifen on the protein kinase C signaling pathway in the frontal cortex and hippocampus of rats submitted to the animal model of mania induced by ouabain. We showed that ouabain induced hyperlocomotion in the rats.


Results
Ouabain increased the protein kinase C activity and the protein kinase C and MARCKS phosphorylation in frontal cortex and hippocampus of rats. Lithium and tamoxifen reversed the behavioral and protein kinase C pathway changes induced by ouabain. These findings indicate that the Na+/K+-ATPase inhibition can lead to protein kinase C alteration.


Conclusions
The present study showed that lithium and tamoxifen modulate changes in the behavior and protein kinase C signalling pathway alterations induced by ouabain, underlining the need for more studies of protein kinase C as a possible target for treatment of bipolar disorder.
['Valvassori|Samira S|SS|', 'Dal-Pont|Gustavo C|GC|', 'Resende|Wilson R|WR|', 'Varela|Roger B|RB|', 'Peterle|Bruna R|BR|', 'Gava|Fernanda F|FF|', 'Mina|Francielle G|FG|', 'Cararo|José H|JH|', 'Carvalho|André F|AF|', 'Quevedo|João|J|']
D000704:Analysis of Variance D000818:Animals D000928:Antidepressive Agents D001714:Bipolar Disorder D001921:Brain D004195:Disease Models, Animal D004333:Drug Administration Routes D004791:Enzyme Inhibitors D008094:Lithium D008124:Locomotion D008297:Male D010042:Ouabain D011493:Protein Kinase C D051381:Rats D017208:Rats, Wistar D013629:Tamoxifen
protein kinase C animal model of mania ouabain Na+/K+-ATPase bipolar disorder