Ouabain, a Na–K-ATPase inhibitor, enhances wakefulness in rats

Abstract

Sleep disturbances are common findings in bipolar affective disorder (BD), and they may be related to the pathophysiology of the disease. REM sleep deprivation, which has an antidepressant effect, increases Na–K-ATPase (NKA) activity. NKA might be involved in the induction of rebound sleep. Decrements in NKA are thought to be implicated in the pathophysiology of BD. A single intracerebroventricular (ICV) microinjection of ouabain (OUA), an NKA inhibitor, results in long-lasting suppression of NKA activity. It has been proposed to be used as a model of BD. To elucidate the role of NKA, we studied the effects of ICV administered OUA on the sleep–wake activity of rats. Rats were ICV injected with saline on the baseline day and 2.5 μL 20 μM (n = 8) or 2 mM (n = 6) OUA on the subsequent OUA day. Saline was administered 1, 4, and 8 days after OUA injection. Sleep–wake activity was recorded for 12 h or 24 h post-injection. OUA enhanced wakefulness, but there was only little similarity between the changes in sleep and in BD after OUA treatment. These findings give only limited support for the NKA hypothesis of BD. Not the decrease in NKA activity itself that may be the important factor in the pathophysiology of BD, but rather the dysfunction of those regulatory processes that influence NKA.