Dissociating effects of spatial learning from locomotor activity for ouabain-induced bipolar disorder-like rats

Wang, Ying Chou; Wang, En Nan; Wang, Chia–Chuan; Huang, Chung Lei; Huang, Andrew Chih Wei

doi:10.1016/j.psychres.2014.03.003

Cited by 5 publications

(4 citation statements)

References 35 publications

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“…A central ouabain injection did not affect acquisition of the spatial discrimination. This differs from results reported by Wang and colleagues (2013, 2014) who found that ICV ouabain treatment impaired acquisition in a water maze test. There are various possibilities that may explain the different results.…”

Section: Discussioncontrasting

confidence: 99%

“…The dose was based on past studies using the same concentration of ouabain (Gao et al, 2011; Varela et al, 2015; Wang et al, 2014). To execute the microinfusion procedure the stylet was first removed from the guide cannula while a rat was restrained.…”

Section: Methodsmentioning

confidence: 99%

“…Consistent with ouabain treatment serving as a model of mania, an intracerebroventricular (ICV) injection of ouabain increases locomotor activity in rats (Brocardo et al, 2010; Decker et al, 2000; Herman et al, 2007; Souza et al, 2014; Varela et al, 2015). However, few studies have examined whether the ouabain model of mania leads to cognitive deficits (Wang et al, 2013, 2014) and even less is known about whether ICV ouabain treatment leads to impairments in working memory and cognitive flexibility.…”

Section: Introductionmentioning

confidence: 99%

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Cognitive flexibility impairment and reduced frontal cortex BDNF expression in the ouabain model of mania

et al. 2017

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Central infusion of the Na+/K+-ATPase inhibitor, ouabain in rats serves as an animal model of mania because it leads to hyperactivity, as well as reproduces ion dysregulation and reduced BDNF levels similar to that observed in bipolar disorder. Bipolar disorder is also associated with cognitive inflexibility and working memory deficits. It is unknown whether ouabain treatment in rats leads to similar cognitive flexibility and working memory deficits. The present study examined the effects of an intracerebral ventricular infusion of ouabain in rats on spontaneous alternation, probabilistic reversal learning and BDNF expression levels in the frontal cortex. Ouabain treatment significantly increased locomotor activity, but did not affect alternation performance in a Y-maze. Ouabain treatment selectively impaired reversal learning in a spatial discrimination task using an 80/20 probabilistic reinforcement procedure. The reversal learning deficit in ouabain-treated rats resulted from an impaired ability to maintain a new choice pattern (increased regressive errors). Ouabain treatment also decreased sensitivity to negative feedback during the initial phase of reversal learning. Expression of BDNF mRNA and protein levels was downregulated in the frontal cortex which also negatively correlated with regressive errors. These findings suggest that the ouabain model of mania may be useful in understanding the neuropathophysiology that contributes to cognitive flexibility deficits and test potential treatments to alleviate cognitive deficits in bipolar disorder.

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Section: Discussioncontrasting

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cognitive flexibility impairment and reduced frontal cortex BDNF expression in the ouabain model of mania

et al. 2017

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“…Several rodent studies have used a pharmacological approach to perturb Na + ,K + -ATPase function in the brain. Intracranial injection of ouabain, a specific Na + ,K + -ATPase inhibitor that does not cross the blood–brain barrier ( Sugimoto et al, 2011 ), has been shown to impair learning and memory in laboratory rats and mice ( Mizumori et al, 1987 ; Sato et al, 2004 ; Tucker & Gibbs, 1979 ; Wang et al, 2013 , 2014 ; Zhan et al, 2004 ). These studies all point to a relationship between inhibition of Na + ,K + -ATPase in the brain and impairment of learning and memory, but they are limited by the similar affinities of the α2 and α3 subunits for ouabain ( Sweadner, 1989 ); thus, precluding Na + ,K + -ATPase α3 specificity.…”

Section: Discussionmentioning

confidence: 99%

Characterization of cognitive deficits in mice with an alternating hemiplegia-linked mutation.

Kirshenbaum¹,

Dachtler²,

Roder³

et al. 2015

Behavioral Neuroscience

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Cognitive impairment is a prominent feature in a range of different movement disorders. Children with Alternating Hemiplegia of Childhood are prone to developmental delay, with deficits in cognitive functioning becoming progressively more evident as they grow older. Heterozygous mutations of the ATP1A3 gene, encoding the Na+,K+-ATPase α3 subunit, have been identified as the primary cause of Alternating Hemiplegia. Heterozygous Myshkin mice have an amino acid change (I810N) in Na+,K+-ATPase α3 that is also found in Alternating Hemiplegia. To investigate whether Myshkin mice exhibit learning and memory deficits resembling the cognitive impairments of patients with Alternating Hemiplegia, we subjected them to a range of behavioral tests that interrogate various cognitive domains. Myshkin mice showed impairments in spatial memory, spatial habituation, locomotor habituation, object recognition, social recognition, and trace fear conditioning, as well as in the visible platform version of the Morris water maze. Increasing the duration of training ameliorated the deficit in social recognition but not in spatial habituation. The deficits of Myshkin mice in all of the learning and memory tests used are consistent with the cognitive impairment of the vast majority of AHC patients. These mice could thus help advance our understanding of the underlying neural mechanisms influencing cognitive impairment in patients with ATP1A3-related disorders.

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Ouabain induces memory impairment and alter the BDNF signaling pathway in an animal model of bipolar disorder

Valvassori¹,

Dal‐Pont²,

Varela³

et al. 2021

Journal of Affective Disorders

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Dissociating effects of spatial learning from locomotor activity for ouabain-induced bipolar disorder-like rats

Cited by 5 publications

References 35 publications

Cognitive flexibility impairment and reduced frontal cortex BDNF expression in the ouabain model of mania

Cognitive flexibility impairment and reduced frontal cortex BDNF expression in the ouabain model of mania

Characterization of cognitive deficits in mice with an alternating hemiplegia-linked mutation.

Ouabain induces memory impairment and alter the BDNF signaling pathway in an animal model of bipolar disorder

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