Effects of Ketamine on Manic/Depressive Behaviors in Homocysteic-acid Treated Rats

Faculty Mentor(s)

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

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Previous work in our laboratory has shown that demonstrated that male and female rats that receive daily intraperitoneal injections of the endogenous, glutamatergic agonist homocysteic acid (HCA) from postnatal day 3-21 develop behaviors that are consistent with a mixed depressive/manic phenotype. Specifically, HCA-treated rats exhibit anhedonia in a saccharine preference test and reduced social interactions consistent with a depressive phenotype. In addition, these animals also exhibit increased locomotion and risk-taking behavior in novel environments and increased goal-directed behavior in the Morris Water Maze. We have previously hypothesized that the behaviors elicited by HCA treatment may suggest that we have developed a novel animal model for bipolar disorder. We have shown that treatment of our model animals with lithium, a drug used in the treatment of bipolar disorder, reversed the manic-like behaviors associated with HCA-exposure. The lithium treatment reduced time the HCA-treated animals spent in the open arms of the elevated plus maze and hyperlocomotive behavior in novel environments. In the current study, we determined if ketamine, a drug that rapidly reverses depression in humans and depressive-like behaviors in rats, would reverse the depressive-like behaviors in HCA-treated animals. We tested the effects of ketamine on motor behavior (Rotarod), hedonistic behavior (sucrose preference), exploratory behavior and anxiety (elevated plus maze), depressive-behavior (forced swim) and social behavior (social interaction) in male and female HCA-treated rats. The results of these tests will be presented and discussed.


This research was supported by the Departments of Biology and Chemistry and the Neuroscience Program at Hope College.

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