, Volume 232, Issue 20, pp 3763–3772 | Cite as

Inhibition of hyperactivity and impulsivity by carbonic anhydrase inhibitors in spontaneously hypertensive rats, an animal model of ADHD

  • Ming-Tao Yang
  • Dai-Hua Lu
  • Jui-Ching Chen
  • Wen-Mei FuEmail author
Original Investigation



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.


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.


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.


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.


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.


Acetazolamide Attention deficit hyperactivity disorder Carbonic anhydrase inhibitor Impulsivity Methazolamide Spontaneously hypertensive rat Locomotor activity 



The authors would like to thank Sau-Pin Won, MD, a native English speaker, for English editing of this manuscript to the standards of the journal. This work was supported by the Ministry of Science and Technology, Taiwan (NSC 102-2321-B-002-065).

Disclosure/conflicts of interest

The authors have no conflict of interest to be declared.

Supplementary material

213_2015_4036_Fig6_ESM.gif (66 kb)
Fig. S1

Photograph of electro-foot shock aversive water drinking test (EFSDT) apparatus. The black Plexiglas box is divided into three compartments (start area, water area, and free area). During the testing phase (day 3), an electro-foot shock (2 mA, 0.5 s from the stimulator) was given whenever the rats licked water from the bottle for at least 5 s. Details of the apparatus and experimental protocol are described in the “Methods” section. (GIF 66 kb)

213_2015_4036_MOESM1_ESM.tif (3.2 mb)
High resolution image (TIFF 3227 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Ming-Tao Yang
    • 1
    • 2
  • Dai-Hua Lu
    • 2
  • Jui-Ching Chen
    • 3
  • Wen-Mei Fu
    • 2
    Email author
  1. 1.Department of PediatricsFar Eastern Memorial HospitalNew Taipei CityTaiwan
  2. 2.Institute of Pharmacology, College of MedicineNational Taiwan UniversityZhongzheng DistrictTaiwan
  3. 3.Department of BotanicalsMedical and Pharmaceutical Industry Technology and Development CenterNew Taipei CityTaiwan

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