title: Effects of methylphenidate on attentional set-shifting in a genetic model of attention-deficit/hyperactivity disorder.
abstract: BACKGROUND
  Although deficits of attentional set-shifting have been reported in individuals with attention deficit/hyperactivity disorder (ADHD), it is rarely examined in animal models.
  
  
  METHODS
  This study compared spontaneously hypertensive rats (SHRs; a genetic animal model of ADHD) and Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats (normoactive control strains), on attentional set-shifting task (ASST) performance. Furthermore, the dose-effects of methylphenidate (MPH) on attentional set-shifting of SHR were investigated. In experiment 1, ASST procedures were conducted in SHR, WKY and SD rats of 8 each at the age of 5 weeks. Mean latencies at the initial phase, error types and numbers, and trials to criteria at each stage were recorded. In experiment 2, 24 SHR rats were randomly assigned to 3 groups of 8 each-- MPH-L (lower dose), MPH-H (higher dose), and SHR-vehicle groups. From 3 weeks, they were administered 2.5 mg/kg or 5 mg/kg MPH or saline respectively for 14 consecutive days. All rats were tested in the ASST at the age of 5 weeks.
  
  
  RESULTS
  The SHRs generally exhibited poorer performance on ASST than the control WKY and SD rats. Significant strain effects on mean latency [F (2, 21) = 639.636, p < 0.001] and trials to criterion [F (2, 21) = 114.118, p < 0.001] were observed. The SHRs were found to have more perseverative and regressive errors than the control strains (p < 0.001). After MPH treatment, the two MPH treated groups exhibited significantly longer latency and fewer trials to reach criterion than the SHR-vehicle group and the MPH-L group exhibited fewer trials to reach criterion in more stages compared with the MPH-H group. Significant main effects of treatment [F (2, 21) = 52.174, p < 0.001] and error subtype [F (2, 42) = 221.635, p < 0.01] were found.
  
  
  CONCLUSIONS
  The SHR may be impaired in discrimination learning, reversal learning and attentional set-shifting. Our study provides evidence that MPH may improve the SHR's performance on attentional set-shifting and lower dose is more effective than higher dose.
authors.affiliation: Department of Pediatrics, Qilu Hospital, Shandong University, Jinan, People's Republic of China.
authors.forename: Ai-hua
authors.initials: AH
authors.lastname: Cao
authors.forename: Lin
authors.initials: L
authors.lastname: Yu
authors.forename: Yu-wei
authors.initials: YW
authors.lastname: Wang
authors.forename: Jun-mei
authors.initials: JM
authors.lastname: Wang
authors.forename: Le-jin
authors.initials: LJ
authors.lastname: Yang
authors.forename: Ge-Fei
authors.initials: GF
authors.lastname: Lei
mesh_terms: D000818:Animals; D001288:Attention / Q000187:drug effects* / Q000502:physiology; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000235:genetics*; D000697:Central Nervous System Stimulants / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology / Q000627:therapeutic use*; D008957:Models, Genetic; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013045:Species Specificity
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate