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

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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.

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Acknowledgments

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.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Far Eastern Memorial Hospital, No. 21, Section 2, Nanya South Road, Banciao District, New Taipei City, 220, Taiwan

    Ming-Tao Yang

  2. Institute of Pharmacology, College of Medicine, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Zhongzheng District, Taipei, 100, Taiwan

    Ming-Tao Yang, Dai-Hua Lu & Wen-Mei Fu

  3. Department of Botanicals, Medical and Pharmaceutical Industry Technology and Development Center, 7F, No. 9, Wuquan Road, Wugu District, New Taipei City, 248, Taiwan

    Jui-Ching Chen

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  1. Ming-Tao Yang
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Correspondence to Wen-Mei Fu.

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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)

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Yang, MT., Lu, DH., Chen, JC. et al. Inhibition of hyperactivity and impulsivity by carbonic anhydrase inhibitors in spontaneously hypertensive rats, an animal model of ADHD. Psychopharmacology 232, 3763–3772 (2015). https://doi.org/10.1007/s00213-015-4036-5

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  • DOI: https://doi.org/10.1007/s00213-015-4036-5

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