Rats tested after a washout period from sub-chronic PCP administration exhibited impaired performance in the 5-choice continuous performance test (5C-CPT) when the attentional load was increased

摘要

It is well documented that schizophrenia patients exhibit dysfunction in various cognitive domains, including attention/vigilance, as demonstrated by impaired performance in the myriad of continuous performance tests (CPTs). NMDA receptor antagonists provide a pharmacological model in animals of the cognitive disruption presented in the disorder. We therefore examined the effects of a sub-chronic PCP treatment regimen (5.0 mg/kg 7-days bi-daily) in the recently developed rodent test of vigilance, the 5 Choice-Continuous Performance Test (5C-CPT). We assessed the effects of this regimen after at least a 7-day washout period on both baseline performance and when the attentional load was increased. Sub-chronic PCP-treatment impaired 5C-CPT performance in a manner consistent with impaired vigilance in patients with schizophrenia, with reduced hit rate and impaired signal sensitivity. These effects were only evident when performance was challenged following parameter manipulations. These data demonstrate that attention/vigilance is sensitive to disruption following sub-chronic PCP treatment in a pre-clinical task that may demonstrate increased analogy to human vigilance tasks. Although the PCP-induced attentional deficits are not as large as those deficits observed in other domains, these data provide evidence that this pharmacological model can affect multiple cognitive domains and may be useful for assessing putative pro-cognitive therapeutics for schizophrenia.