Parvizi, Mahsa2010-08-062010-08-062010-05http://udspace.udel.edu/handle/19716/5508Schizophrenia is a chronic, debilitating psychiatric disorder that affects approximately 1% of the world’s population. A leading hypothesis of the etiology of this disorder suggests dysfunction at glutamate synapses. The current study utilized infusion of MK801, an NMDA (glutamate receptor)-antagonist, into the medial-prefrontal cortex (mPFC), a brain region that is impaired in schizophrenia. The first goal of the current project (Experiment 1) was to ascertain whether a correlation exists between behavioral flexibility and working memory impairments in MK801-treated rats. Behavioral flexibility was assessed with an attentional set-shifting task (ASST), followed by a delayed non-match-to-position (DNMP) working memory task. The second experiments (Experiment 2) involved the effects of MK801on the ASST and the specific dimension(s) of the task that was most impaired in treated rats. A non-significant positive correlation was observed between the first reversal (Rev1) of the ASST and day 1 of the DNMP task. In relations to Experiment 2, significant impairment (increased trials to criterion and errors) was seen in the reversal (Rev3) of the extradimensional shift (EDS) of the ASST among the MK801 treated rats compared to the saline rats. This result contradicts previous studies with mPFC-lesioned rats, which showed most deficits in the EDS and not its reversal. These results should be further studied with a larger population of rats to promote a deeper understanding of the mechanism behind this aberrant psychotic disorder.Schizophrenia -- Animal modelsDizocilpineGlutamic acid -- ReceptorsPrefrontal cortexRats -- DiseasesThesis