Persistent Hyperactivity Following a Single Intracerebroventricular Dose of Ouabain

Intracerebral Administration of BDNF Protects Rat Brain Against Oxidative Stress Induced by Ouabain in an Animal Model of Mania

“…In the present study, we demonstrated that ICV ouabain administration increased locomotor activity and risk-taking behavior in rats, which are considered manic-like behaviors, replicating data from our and many other laboratories [18,33,45,46]. Animal model of human disease should meet three sets of criteria as follows: have similar behavioral manifestations as the human disease (face validity), share pathophysiological characteristics of the human condition (construct validity), and reversed and/or prevented with medications that improve the symptoms seen in afflicted humans (predictive validity) [31].…”

Mania-like behavior induced by genetic dysfunction of the neuron-specific Na + ,K + -ATPase α3 sodium pump

“…All human α-isoforms and rodent α2 and α3 isoforms, have a high binding affinity for endogenous OLCs, which regulate Na + ,K + -ATPase activity and initiate signaling (4)(5)(6). Intracerebroventricular (ICV) administration of ouabain to rats stimulates locomotor hyperactivity and NKA signaling and is considered as a model of mania (7)(8)(9), but the similar affinities of α2 and α3 for ouabain have precluded conclusive pharmacological studies of isoform specificity.…”

Sodium butyrate and mood stabilizers block ouabain-induced hyperlocomotion and increase BDNF, NGF and GDNF levels in brain of Wistar rats

“…Intracerebroventricular (ICV) injection of ouabain induced hyperactivity in rats by inhibiting Na þ /K þ -ATPase El-Mallakh and Wyatt, 1995;El-Mallakh et al, 2003), and it has been suggested a relevant animal model of mania (MachadoVieira et al, 2004;Young et al, 2011). In addition, previous studies have demonstrated that the manic-like behavior induced by ouabain remained up to 7 days following a single ICV injection (Riegel et al, 2009;Ruktanonchai et al, 1998). These observations strength the view that ouabain-induced mania-like behavior in rats could be a useful model to investigate some aspects linked to the chronicity of BD, such as long-term neurochemical alterations.…”