Inhibition of hyperactivity and impulsivity by carbonic anhydrase inhibitors in spontaneously hypertensive rats, an animal model of ADHD
Journal
Psychopharmacology
Journal Volume
232
Journal Issue
20
Pages
3763-3772
Date Issued
2015
Author(s)
Abstract
Rationale: 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. Objectives: 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. ? 2015 Springer-Verlag Berlin Heidelberg.
Subjects
Acetazolamide; Attention deficit hyperactivity disorder; Carbonic anhydrase inhibitor; Impulsivity; Locomotor activity; Methazolamide; Spontaneously hypertensive rat
Other Subjects
acetazolamide; atomoxetine; methazolamide; methylphenidate; acetazolamide; carbonate dehydratase inhibitor; animal experiment; animal model; Article; attention deficit disorder; aversive behavior; behavior disorder; controlled study; dose response; drug efficacy; footshock; hyperactivity; hypertension; impulsiveness; locomotion; low drug dose; male; Morris water maze test; nonhuman; open field behavior; priority journal; rat; spatial learning; animal; Attention Deficit Disorder with Hyperactivity; disease model; drug effects; human; Hyperkinesis; impulsiveness; motor activity; pathophysiology; physiology; spontaneously hypertensive rat; Wistar Kyoto rat; Acetazolamide; Animals; Attention Deficit Disorder with Hyperactivity; Carbonic Anhydrase Inhibitors; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Hyperkinesis; Impulsive Behavior; Male; Motor Activity; Rats; Rats, Inbred SHR; Rats, Inbred WKY
Type
journal article