title: D₁ receptor activation improves vigilance in rats as measured by the 5-choice continuous performance test.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: School of Pharmacy, University of Bradford, Bradford, West Yorkshire, BD7 1DP, UK.
authors: Samuel A
authors: SA
authors: Barnes
authors: Jared W
authors: JW
authors: Young
authors: Jo C
authors: JC
authors: Neill
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001288:Attention / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D023421:Models, Animal; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000819:agonists* / Q000378:metabolism
chemical_list: D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine