Homocysteine Exposure in Early Postnatal Rats Leads to an Incomplete Bipolar Disorder Phenotype

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Dr. Leah A. Chase, Neuroscience Program and Departments of Biology and Chemistry

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Elevated levels of plasma homocysteine have been linked to neuropsychiatric disorders such as Bipolar Disorder. Therefore, we sought to determine if homocysteine itself would lead to a bipolar-like phenotype. We fed lactating rats either a high homocysteine/low vitamin B diet (HCY) or a standard rat diet, and examined the behavioral effects on the offspring. We assessed the rats for altered risk-taking behavior, activity level, anhedonia, learned helplessness, social behavior, goal-oriented motivation and spatial learning. In the elevated plus maze, we observed a significant increase in time spent and distance traveled in open arms of HCY rats compared to control rats, suggesting increased risk-taking behavior. We did not observe hyperactivity in the HCY rats in the elevated plus maze, wheel running assay, or social interaction test. In the saccharin preference test, HCY-treated rats consumed a significantly lower saccharin:water ratio than control rats, demonstrating anhedonia. We did not observe any differences in learned helplessness in the forced swim test between control and HCY treated animals. There was no effect of HCY treatment on social interaction; however, the HCY treated animals spent significantly more time interacting with both cages in the first trial than control rats, suggesting increased curiosity. There was no effect of HCY on goal-oriented motivation and/or spatial learning in the first day of Morris Water Maze testing. However, HCY treated animals took significantly longer to complete the maze on the first trial of day two, suggesting HCY reduced spatial memory. These results suggest elevated HCY triggers features of Bipolar Disorder such as anhedonia and increased risk-taking behavior. However, exposure to HCY did not elicit hyperactivity, learned helplessness, increased goal-oriented behavior, or altered social behavior, implying that HCY alone is not sufficient to produce a complete bipolar-like phenotype.

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