Effect of Lithium Treatment on Homocysteic Acid-Induced Manic/Depressive Behaviors in Sprague-Dawley Rats

Faculty Mentor(s)

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

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Bipolar disorder is a mood disorder for which the development of new treatments has been hindered by the lack of a reliable animal model. Previous studies in our lab have shown that daily injection of early postnatal rat pups with homocysteic acid (HCA), a homocysteine metabolite, leads to a mixed manic/depressive phenotype in adulthood. These results suggest that early HCA exposure may serve as a good model for bipolar disorder. To test the predictive validity of this model, we sought to determine if treatment of HCA-exposed animals with lithium was effective in reducing mixed manic/depressive behaviors elicited by HCA. As predicted, lithium treatment resulted in diminished manic-like behaviors in the HCA-treated rats and restored spatial learning in the Morris water maze of female, HCA-treated rats. Lithium also increased saccharine preference in female, HCA-treated animals and social activity in male, HCA-treated animals. However, lithium caused a reduction in saccharine preference and social behavior in the saline-treated rats. Finally, to determine if the effects of lithium were reversible, we removed the lithium from the rats’ diet for ten days and repeated the behavioral assessment. Removal of lithium resulted in the re-establishment of manic behavior in the elevated plus maze and a reduction of spatial learning in HCA-treated rats. However, the effects of lithium on the depression-associated behaviors of HCA-treated animals were not reversed, and all animals exhibited a strong increase saccharine preference and social behavior compared to when they were fed lithium. Thus, our results suggest that lithium is effective in treating the manic behavior, spatial learning deficits, anhedonia and reduced social interaction elicited by HCA as hypothesized. Collectively, these data provide further evidence that early postnatal exposure to HCA may serve as model for the mixed manic/depressive phenotype associated with bipolar disorder.


This work was funded by the Hope College Neuroscience Program, and the Departments of Biology and Chemistry.

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