Five-choice serial reaction time task performance following catecholamine depletion of rat medial prefrontal cortex: implications for attention deficit in schizophrenia
The symptoms of schizophrenia are highly variable and include a variety of cognitive deficits, including attentional deficit. These cognitive deficits may involve dopamine (DA) underactivity in the prefrontal cortex (PFC) (Weinberger, Egan, Bertolino, Callicott, Mattay, Lipska, et al., 2001). The purpose of this thesis was to test the hypothesis that reduced DA in the PFC alters attention by examining the effects of reduced DA in the medial PFC (mPFC) of rats on a sustained attention task. Rats in the DA-lesioned group were administered 6-hydroxydopamine (6-OHDA) in the mPFC. Following 6-OHDA administration, rats in the DA-lesioned and shamlesioned group were trained to nose poke into a lit aperture for food reward in the 5-choice serial reaction time task (5-CSRTT), a rodent analogue of the Continuous Performance Task used to assess sustained attention in schizophrenics (Robbins, 2002). The 6-OHDA administration resulted in depletions of both DA (33% of controls) and norepinephrine (NE) (50% of controls). Rats\u27 performance was assessed by comparing the frequency of correct, incorrect, omitted, and premature responses in testing conditions where the duration of stimulus in the 5-CSRTT was randomly varied from 2.5 to 0.25 seconds. No significant differences between lesioned and control rats were observed in any behavioral testing parameters. However, there was a trend toward increased numbers of omissions and reduced correct responses seen in lesioned rats especially at the shortest stimulus durations. The trend supports the hypothesis that reduced DA in the PFC contributes to attentional dysfunction in schizophrenia. Future studies should examine the behavioral effects of 6-OHDA lesions using larger sample sizes. Also, future studies should examine rats\u27 5-CSRTT performance at stimulus durations less than 0.25 seconds to further explore the trend toward poorer performance seen in 6-OHDA lesioned rats
