Effects of MK801 on attentional flexibility in a rodent model of schizophrenia
Date
2010-05
Authors
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Journal ISSN
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Publisher
University of Delaware
Abstract
Schizophrenia 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.