Does Lithium Diminish Manic/Depressive Behaviors in Rats Associated with HCA Exposure?

Faculty Mentor(s)

Dr. Leah Chase

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The development of novel treatments for Bipolar Disorder has been hampered by the lack of a good animal model for the disease. The purpose of this study was to establish predictive validity for a novel animal model for bipolar disorder. Previous work in Dr. Chase’s lab has demonstrated that early exposure to the glutamatergic agonist, homocysteic acid (HCA), leads to a phenotype which is consistent with a mixed manic/depressive state as is often observed with bipolar disorder. Specifically, we observed that HCA-treated rats displayed increased risk-taking behavior, reduced social behavior, novelty-induced hyperlocomotion, anhedonia, and increased motivational behavior compared to control rats. Now we wish to determine if lithium, a common treatment for bipolar disorder, will lead to a reduction in depressive and manic behaviors associated with HCA. Therefore, we injected 23 rats daily with the endogenous, glutamatergic agonist homocysteic acid (HCA) from postnatal days 3-21. Another group of 23 rats received injection of saline. Six weeks later, the saccharine preference test, elevated plus maze, social interaction test, rotarod test, forced swim test and Morris Water Maze were conducted to assess anhedonia, risk taking behavior, social interaction, motor coordination, depressive behaviors, motivation and risk-taking behaviors. The rats were then treated with lithium for the remainder of the experiment and assessed in the same behavioral tests described previously to observe whether lithium was effective in reducing the behaviors associated with HCA exposure. If lithium is found to reduce manic and depressive behaviors in HCA-treated rats, this would suggest that the HCA model could potentially be used to identify novel pharmacological agents that would better treat the disorder.

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