title: Inhibition of hyperactivity and impulsivity by carbonic anhydrase inhibitors in spontaneously hypertensive rats, an animal model of ADHD.
abstract: BACKGROUND
  Dysregulation of noradrenergic and dopaminergic systems is involved in the pathology of attention deficit hyperactivity disorder (ADHD). Carbonic anhydrase (CA) has been reported to affect monoamine transmission in the central nervous system.
  
  
  OBJECTIVE
  The aim of this study is to investigate the effect of CA inhibitors on the hyperactivity and impulsivity of the spontaneously hypertensive rat (SHR), which is currently the best-validated animal model of ADHD.
  
  
  METHODS
  SHRs and Wistar Kyoto rats at 6 to 8 weeks of age were pretreated with intraperitoneal injections of acetazolamide and methazolamide, both carbonic anhydrase inhibitors, before the behavior tests. The open-field locomotion test and the electro-foot shock aversive water drinking test were then applied to quantify their hyperactivity and impulsivity, respectively. The Morris water maze test, on the other hand, monitored their spatial learning.
  
  
  RESULTS
  Acetazolamide and methazolamide significantly inhibited the hyperactivity of SHRs but had no effects in Wistar Kyoto rats. Acetazolamide also inhibited the impulsivity of SHRs. Low doses of acetazolamide had the greater inhibitory effects on the hyperactivity and impulsivity, but did not impair the spatial learning of SHRs.
  
  
  CONCLUSIONS
  This is the first study to show that carbonic anhydrase inhibitors can strain-specifically antagonize the hyperactivity and impulsivity of SHRs. Under a low dose of acetazolamide, there was no cognition impairment in SHRs. Carbonic anhydrase inhibitors may be the novel drugs for treatment for patients with ADHD.
authors.affiliation: Department of Pediatrics, Far Eastern Memorial Hospital, No. 21, Section 2, Nanya South Road, Banciao District, New Taipei City, 220, Taiwan.
authors.forename: Ming-Tao
authors.initials: MT
authors.lastname: Yang
authors.forename: Dai-Hua
authors.initials: DH
authors.lastname: Lu
authors.forename: Jui-Ching
authors.initials: JC
authors.lastname: Chen
authors.forename: Wen-Mei
authors.initials: WM
authors.lastname: Fu
mesh_terms: D000086:Acetazolamide / Q000627:therapeutic use; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000503:physiopathology; D002257:Carbonic Anhydrase Inhibitors / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006948:Hyperkinesis / Q000188:drug therapy* / Q000503:physiopathology; D007175:Impulsive Behavior / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D000086:Acetazolamide