Effects of Ketamine on Manic/Depressive Behaviors in Homocysteic-acid Treated Rats
Dr. Christopher Barney, Department of Biology, Dr. Leah Chase, Neuroscience Program and Departments of Biology and Chemistry
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.
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