Lithium prevents ouabain-induced behavioral changes

Li, Rena; El‐Mallakh, Rif S.; Harrison, Linda T.; Changaris, David G.; Levy, Robert S.

doi:10.1007/bf02815161

Cited by 60 publications

(7 citation statements)

References 10 publications

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“…Regarding the presented evidence, OUA ICV injection in rats could be a candidate to a putative experimental model of BD by reproducing specific pathophysiological mechanisms of the disorder and simulate the related mood swings 13,16 . However, further tests are required for the validation of the model.…”

Section: Introductionmentioning

confidence: 81%

“…Intracerebroventricular (ICV) injection of this glycoside in rats also induces hypoactivity, which could be considered a depressive-like behavior. Such behavioral alterations are significantly prevented by administration of lithium (Li), an important mood stabilizer 13,16 . However, hypoactivity is not enough to mimic a state of depression, and additional experiments are necessary to validate this model.…”

Section: Introductionmentioning

confidence: 99%

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Validation of the animal model of bipolar disorder induced by Ouabain: face, construct and predictive perspectives

Valvassori¹,

Dal‐Pont²,

Resende³

et al. 2019

Transl Psychiatry

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A particular challenge in the development of a bipolar disorder (BD) model in animals is the complicated clinical course of the condition, characterized by manic, depressive and mixed mood episodes. Ouabain (OUA) is an inhibitor of Na + /K + -ATPase enzyme. Intracerebroventricular (ICV) injection of this drug in rats has been regarded a proper model to study BD by mimic specific manic symptoms, which are reversed by lithium (Li), an important mood stabilizer drug. However, further validation of this experimental approach is required to characterize it as an animal model of BD, including depressive-like behaviors. The present study aimed to assess manic- and depressive-like behaviors, potential alteration in the hypothalamic-pituitary-adrenal (HPA) system and oxidative stress parameters after a single OUA ICV administration in adult male Wistar rats. Moreover, we evaluated Li effects in this experimental setting. Data show that OUA ICV administration could constitute a suitable model for BD since the injection of the drug triggered manic- and depressive-like behaviors in the same animal. Additionally, the OUA model mimics significant physiological and neurochemical alterations detected in BD patients, including an increase in oxidative stress and change in HPA axis. Our findings suggest that decreased Na + /K + -ATPase activity detected in bipolar patients may be linked to increased secretion of glucocorticoid hormones and oxidative damage, leading to the marked behavioral swings. The Li administration mitigated these pathological changes in the rats. The proposed OUA model is regarded as suitable to simulate BD by complying with all validities required to a proper animal model of the psychiatric disorder.

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Section: Introductionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Validation of the animal model of bipolar disorder induced by Ouabain: face, construct and predictive perspectives

Valvassori¹,

Dal‐Pont²,

Resende³

et al. 2019

Transl Psychiatry

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“…Considering the literature suggesting that dopamine-related genes such as some polymorphisms of the dopamine transporter gene are uniquely expressed in BD [31], altered dopamine tone may be an important neurobiological feature of the illness of BD and not unique to manic episodes Furthermore, our findings suggest that acute administration of medications in animals may not be the most appropriate way to validate animal models of mania. For example, acute [32], [33], [34], [35] but not chronic [36], [37] lithium reversed stimulant-induced hyperactivity. Given that hyperactivity in manic BD humans is not significantly reversed with acute treatment, these existing animal models of BD require further refinement and validation [38].…”

Section: Discussionmentioning

confidence: 96%

Repeated Assessment of Exploration and Novelty Seeking in the Human Behavioral Pattern Monitor in Bipolar Disorder Patients and Healthy Individuals

et al. 2011

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BackgroundExploration and novelty seeking are cross-species adaptive behaviors that are dysregulated in bipolar disorder (BD) and are critical features of the illness. While these behaviors have been extensively quantified in animals, multivariate human paradigms of exploration are lacking. The human Behavioral Pattern Monitor (hBPM), a human version of the animal open field, identified a signature pattern of hyper-exploration in manic BD patients, but whether exploratory behavior changes with treatment is unknown. The objective of this study was to assess the sensitivity of the hBPM to changes in manic symptoms, a necessary step towards elucidating the neurobiology underlying BD.Methodology and Principal FindingsTwelve acutely hospitalized manic BD subjects and 21 healthy volunteers were tested in the hBPM over three sessions; all subjects were retested one week after their first session and two weeks after their second session. Motor activity, spatial and entropic (degree of unpredictability) patterns of exploration, and interactions with novel objects were quantified. Manic BD patients demonstrated greater motor activity, extensive and more unpredictable patterns of exploration, and more object interactions than healthy volunteers during all three sessions. Exploration and novelty-seeking slightly decreased in manic BD subjects over the three sessions as their symptoms responded to treatment, but never to the level of healthy volunteers. Among healthy volunteers, exploration did not significantly decrease over time, and hBPM measures were highly correlated between sessions.Conclusions/SignificanceManic BD patients showed a modest reduction in symptoms yet still demonstrated hyper-exploration and novelty seeking in the hBPM, suggesting that these illness features may be enduring characteristics of BD. Furthermore, behavior in the hBPM is not subject to marked habituation effects. The hBPM can be reliably used in a repeated-measures design to characterize exploration and novelty seeking and, in parallel with animal studies, can contribute to developing treatments that target neuropsychiatric disease.

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“…Furthermore, repeated exposure to an open-field chamber may induce a ‘floor effect’, where activity levels are so low that a drug effect alone could not lower them further. For example, Li et al (1997) habituated rats for several days in the open field prior to quantifying ouabain-induced hyperactivity and acute lithium ‘reversal’ of effects. Lithium failed to decrease activity levels in this study since they were already minimal due to environmental familiarity (Li et al, 1997).…”

Section: Pharmacological Models Of Maniamentioning

confidence: 99%

Animal models of bipolar mania: The past, present and future

2016

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Bipolar disorder (BD) is the sixth leading cause of disability in the world according to the World Health Organization and affects nearly 6 million (~2.5% of the population) adults in the United State alone each year. BD is primarily characterized by mood cycling of depressive (e.g., helplessness, reduced energy and activity, and anhedonia) and manic (e.g., increased energy and hyperactivity, reduced need for sleep, impulsivity, reduced anxiety and depression), episodes. The following review describes several animal models of bipolar mania with a focus on more recent findings using genetically modified mice, including several with the potential of investigating the mechanisms underlying ‘mood’ cycling (or behavioral switching in rodents). We discuss whether each of these models satisfy criteria of validity (i.e., face, predictive, and construct), while highlighting their strengths and limitations. Animal models are helping to address critical questions related to pathophysiology of bipolar mania, in an effort to more clearly define necessary targets of first-line medications, lithium and valproic acid, and to discover novel mechanisms with the hope of developing more effective therapeutics. Future studies will leverage new technologies and strategies for integrating animal and human data to reveal important insights into the etiology, pathophysiology, and treatment of BD.

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Lithium prevents ouabain-induced behavioral changes

Cited by 60 publications

References 10 publications

Validation of the animal model of bipolar disorder induced by Ouabain: face, construct and predictive perspectives

Validation of the animal model of bipolar disorder induced by Ouabain: face, construct and predictive perspectives

Repeated Assessment of Exploration and Novelty Seeking in the Human Behavioral Pattern Monitor in Bipolar Disorder Patients and Healthy Individuals

Animal models of bipolar mania: The past, present and future

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