Ouabain induction of cycling of multiple spike responses in hippocampal slices is delayed by lithium.

Alterations in sodium- and potassium-activated adenosine triphosphatase (Na,K-ATPase) activity have been associated with changes of mood states and lithium treatment in bipolar illness. We examined the effects of ouabain and lithium on evoked population responses in rat hippocampal slices. In vitro 3.3 μM ouabain induced cycling between epliptiform activity and unresponsiveness in 18.5% of slices. In vitro ouabain, at 1–10 μM, induced epileptiform multiple spike responses. In vivo lithium pretreatment for 10–21 days produced a significant delay in the onset of this ouabain-induced epileptiform activity compared to control animals. These findings are consistent with other work which suggests that Na,K-ATPase inhibition can both activate and suppress excitable tissues and that lithium pretreatment can mitigate these effects. The implications of these results and others regarding the pathophysiology of bipolar illness are discussed.