Postnatal Injection Of Homocysteic Acid In Rats Leads To The Development Of Schizophrenia-like Behaviors
(Meeting Abstract Supplement)
Hypofunction of N-methyl-D-aspartate receptors (NMDA) in GABAergic interneurons is likely an important factor in the development of schizophrenia. The NMDA receptor agonist, homocysteic acid (HCA), is known to cause cytotoxicity in NMDA-receptor containing neurons. In addition, HCA is a substrate for the cystine/glutamate exchanger, system xc–. While system xc– has broad distribution, it is known to be expressed at the blood brain barrier and GABAergic interneurons of the hippocampus. We hypothesized HCA may be selectively concentrated in GABAergic interneurons by System xc–, thus increasing the susceptibility of these interneurons to NMDA-mediated excitotoxicity by HCA. To test this hypothesis, we performed daily intraperitoneal (IP) injections of either HCA or saline in postnatal rats for 14 days beginning at day P2. Six weeks later, we observed HCA-treated rats displayed increased risk-taking behavior, mild anhedonia, deficits in prepulse inhibition, and increased sensitivity to pain compared to control rats, but no difference in motor performance or weight gain over the course of the experiment. These data suggest that exposure to HCA during early development leads to behavioral changes that are consistent with a schizophrenia phenotype. This research was supported by the Hope College Neuroscience Program, Biology Department and Chemistry Department, and NSF-REU # 0851194.