Intracerebroventricular administration of ouabain as a model of mania in rats

Background: Human bipolar illness is characterized by mood state- and diagnosis-associated abnormalities of cellular cation distribution and transport. These include reduced sodium pump activity and expression and increased intracellular sodium. If these alterations are related to the pathophysiology of the disease, rather than secondary or ancillary abnormalities, then one would expect that modeling of these changes in vivo would produce lithium-preventable behavioral abnormalities. Methods: Ouabain, a potent inhibitor of the sodium pump, was administered intracerebroventricularly to male rats previously fed lithium-containing food or plain rat chow. Locomotion was then quantified in an open field. Results: Ouabain increased locomotion 300% over baseline. Lithium pretreatment prevented the ouabain-induced hyperlocomotion response. Conclusion: Inhibition of central nervous system sodium pump with ouabain produces a plausible animal model of mania. This model may be useful for preclinical screening of potential mood stabilizers.