D 1 receptor activation improves vigilance in rats as measured by the 5-choice continuous performance test

Rationale Impaired attention/vigilance is putatively core to schizophrenia. The dopaminergic D 1 receptor system has been reported as one of the most promising targets for improving cognition in patients with schizophrenia, with some evidence suggesting D 1 activation may improve sustained attention. Objectives The purpose of this study was twofold: firstly assessing the applicability of using rats in the 5-Choice Continuous Performance Test (5 C-CPT), recently validated in mice. Secondly, the effect of systemic administration of a D 1 partial agonist, SKF 38393, on task performance during baseline, and a challenge session consisting of a reduced event-rate was investigated. Methods Animals were trained to perform the 5 C-CPT with performance assessed following systemic SKF 38393 (2, 4 and 6 mg/kg) vs. vehicle administration. Results Rats could discriminate between target (requiring a response) and non-target (requiring the inhibition of response) trials within the 5 C-CPT. Moreover, SKF 38393 treatment impaired performance during the baseline session reducing target detection, yet improved performance during the reduced event-rate challenge session, increasing target detection and improving signal discrimination indicating an SKF 38393-induced enhancement of vigilance. Thus, these data suggest that activation of the D 1 system affected 5 C-CPT performance in a baseline dependent manner. Conclusion Rats can be trained to perform the 5 C-CPT, appropriately withholding from responding to non-target trials. Systemic administration of SKF 38393 impaired performance during baseline conditions. Following a task-related challenge, which reduced the event rate, activation of the dopamine (DA) D 1 system improved performance by heightening the animals' vigilance levels, quantified using signal detection theory. © 2011 Springer-Verlag.