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

Abstract

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 (5.0mg/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.

Fig 1

Performance displayed over the duration of the session following an acute behavioural challenge consisting of introducing a variable SD. T1 – T3 refers to the trial banks, each consisting of 40 trials. Data were expressed as observed mean ± SEM and analysed by two-way repeated measures ANOVA (Trial as within-subjects factor and Treatment as between-subjects factor) followed by Planned Comparisons on the predicted means. # denotes p<0.05 compared to vehicle (2.5 mg/kg PCP). * denotes p<0.05, ** denotes p<0.01, *** denotes p < 0.001 compared to vehicle (5 mg/kg PCP).

Fig 2

Sensitivity Index displayed for each individual stimulus durations presented throughout the session. Data displayed as observed mean ± SEM and analysed by two-way repeated measures ANOVA (SD as within-subjects factor and Treatment as between-subjects factor) followed by Planned Comparisons on the predicted means. The effect of SD on SI was analysed specifically for control animals via one-way repeated measures ANOVA (SD as within-subjects factor) followed by Planned Comparisons. * denotes SI for 0.25 s SD significantly reduced compared to 1 s SD.

Fig 3

Performance displayed over the duration of the session that was extended to 256 trials. T1 – T4 refers to the trial banks, each consisting of 64 trials. Data were expressed as observed mean ± SEM and analysed by two-way repeated measures ANOVA (Trial as within-subjects factor and Treatment as between-subjects factor) followed by Planned Comparisons on the predicted means. # denotes p<0.05 and ## denotes p<0.01 compared to vehicle (2.5 mg/kg PCP). * denotes p<0.05 and ** denotes p<0.01, compared to vehicle (5 mg/kg PCP).

Fig 4

Sensitivity Index (SI) of control animals following the extended session challenge. T1 – T4 refers to the trial banks each consisting of 64 trials. Data were expressed as observed mean ± SEM and analysed by one-way repeated measures (Trial as within-subjects factor) ANOVA followed by Planned Comparisons. * denotes p<0.05 Trial bank 2 (65 – 128) significantly greater than Trial bank 4 (193 – 256).