Cognitive flexibility impairment and reduced frontal cortex BDNF expression in the ouabain model of mania. (14th March 2017)

• Record Type: Journal Article
• Authors: Amodeo, Dionisio A.; Grospe, Gena; Zang, Hui; Dwivedi, Yogesh; Ragozzino, Michael E.
• Is Part Of: Neuroscience. Volume 345(2017)
• Page Start: 229
• Page End: 242
• Publication Date: 2017-03-14
• Subjects: BDNF brain-derived neurotrophic factor -- ECL enhanced chemiluminescence -- ICV intracerebroventricular -- SDS sodium dodecyl sulfate; bipolar disorder -- ouabain -- reversal learning -- working memory -- BDNF -- frontal cortex; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2016.05.058
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Ouabain treatment impairs probabilistic reversal learning. Ouabain treatment increases regressive errors during reversal learning. Ouabain treatment reduces BDNF expression levels in the frontal cortex. There is a negative correlation with regressive errors and frontal cortex BDNF levels. Abstract: 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 brain-derived neurotrophic factor (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.