title: Impulsiveness, overactivity, and poorer sustained attention improve by chronic treatment with low doses of l-amphetamine in an animal model of Attention-Deficit/Hyperactivity Disorder (ADHD).
abstract: BACKGROUND
  ADHD is currently defined as a cognitive/behavioral developmental disorder where all clinical criteria are behavioral. Overactivity, impulsiveness, and inattentiveness are presently regarded as the main clinical symptoms. There is no biological marker, but there is considerable evidence to suggest that ADHD behavior is associated with poor dopaminergic and noradrenergic modulation of neuronal circuits that involve the frontal lobes. The best validated animal model of ADHD, the Spontaneously Hypertensive Rat (SHR), shows pronounced overactivity, impulsiveness, and deficient sustained attention. The primary objective of the present research was to investigate behavioral effects of a range of doses of chronic l-amphetamine on ADHD-like symptoms in the SHR.
  
  
  METHODS
  The present study tested the behavioral effects of 0.75 and 2.2 mg l-amphetamine base/kg i.p. in male SHRs and their controls, the Wistar Kyoto rat (WKY). ADHD-like behavior was tested with a visual discrimination task measuring overactivity, impulsiveness and inattentiveness.
  
  
  RESULTS
  The striking impulsiveness, overactivity, and poorer sustained attention seen during baseline conditions in the SHR were improved by chronic treatment with l-amphetamine. The dose-response curves were, however, different for the different behaviors. Most significantly, the 0.75 mg/kg dose of l-amphetamine improved sustained attention without reducing overactivity and impulsiveness. The 2.2 mg/kg dose improved sustained attention as well as reduced SHR overactivity and impulsiveness.
  
  
  CONCLUSIONS
  The effects of l-amphetamine to reduce the behavioral symptoms of ADHD in the SHR were maintained over the 14 days of daily dosing with no evidence of tolerance developing.
authors: Institute of Basic Medical Sciences, Department of Physiology, University of Oslo, Blindern, NO-0317 Oslo, Norway. terje.sagvolden@medisin.uio.no
authors: Terje
authors: T
authors: Sagvolden
mesh_terms: D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001288:Attention / Q000187:drug effects*; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000188:drug therapy* / Q000523:psychology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D006948:Hyperkinesis / Q000150:complications / Q000188:drug therapy*; D007175:Impulsive Behavior / Q000150:complications / Q000188:drug therapy*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D000661:Amphetamine