Homocysteic Acid Treatment in Rats to Determine Gender Differences and Possible Development of a Novel Schizophrenic Model

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Dr. Christopher Barney, Hope College

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Schizophrenia is a universal and debilitating disease with approximately 1 out of every 100 people experiencing symptoms at some point during their lifetime. Although the etiology of the disorder remains elusive and is believed to be complex and multi factorial, the positive psychotic symptoms of the disorder are believed to arise from disruptions in the dopamine neurotransmitter system, of which the glutamatergic neurotransmitter system is responsible for inhibiting. It has been found that schizophrenics have high circulating levels of the chemical homocysteine, which is the precursor to homocysteic acid. Homocysteic acid (HCA) is known to be taken up by the trafficking System xc-, where it is sequestered then slowly released, resulting in excitatory toxicity in NMDA receptors. The death of these dopamine-inhibiting cells could potentially result in an overactive dopamine system, leading to the development of schizophrenic-like symptoms. In this study we aimed to not only evaluate the efficacy of HCA administration as a schizophrenic model, but also whether there are sex-specific HCA effects as well as general behavioral differences between the sexes. Specifically, we evaluated the effects of sex and HCA treatment on social behavior, cognitive functioning and spatial learning and memory, anxiety level, sensorimotor gating and habituation, motor movement and coordination, hedonistic drives, and body weight by first performing intracerebroventricular injects of HCA and subsequent behavioral analyses. Although our results do not indicate a significant effect of HCA on these measurements of schizophrenic-like symptoms, there were expected sex-dependent and other previously documented outcomes. Further studies using a larger sample size and refined experimental techniques would be beneficial in determining the efficacy of elevated HCA as a model for schizophrenic-like symptoms.

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