Effect of Homocysteic Acid Exposure on NMDA Receptor Expression in Developing Rat Pups

Homocysteic acid (HCA), a NMDA receptor agonist, is an endogenous compound formed from the oxidation of homocysteine. Since hyperhomocysteinemia is a risk factor for several neuropsychiatric disorders, including bipolar disorder and major depressive disorder (MDD), we sought to test the hypothesis that elevated HCA levels in developing rats may induce alterations in NMDA receptor expression and the development of behaviors associated with MDD and/or bipolar disorder. Previously, postnatal male and female rats were injected daily with either HCA or saline from day P3 to P17. The female, HCA-treated rats displayed increased risk-taking behavior, reduced social behavior, novelty-induced hyperlocomotion, anhedonia, and reduced sensitivity to pain compared to control and male-HCA treated rats. Additionally, an increase in NMDAR2 expression was observed in the cortex and hippocampus of female rats. More recently we expanded the injection period from day P3 to P21. Both male and female rats exhibited decreased social interaction, increased anhedonia, and increased risk-taking behaviors. Also, male HCA-treated rats exhibited an increased motivational behavior in the Morris Water Maze and a reduction in food consumption. We did not observe a significant difference in the NMDAR2 expression in the cortex among the HCA-treated and control rats. We also did not observe a difference in receptor levels among males and females. There was a trend for female HCA treated rats to have decreased NMDAR2 expression. Currently, we are working to determine if these differences stem from regional differences of NMDA receptors in the cortex. We would like to acknowledge the students in the Introduction to Neuroscience course in the spring of 2015 for their work testing these rats