Inhibition of hyperactivity and impulsivity by carbonic anhydrase inhibitors in spontaneously hypertensive rats, an animal model of ADHD
- 471 Downloads
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.
KeywordsAcetazolamide 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.
- Cortese S, Holtmann M, Banaschewski T, Buitelaar J, Coghill D, Danckaerts M, Dittmann RW, Graham J, Taylor E, Sergeant J (2013) Practitioner review: current best practice in the management of adverse events during treatment with ADHD medications in children and adolescents. J Child Psychol Psychiatry 54:227–246CrossRefPubMedGoogle Scholar
- Kim P, Choi I, Pena IC, Kim HJ, Kwon KJ, Park JH, Han SH, Ryu JH, Cheong JH, Shin CY (2012) A simple behavioral paradigm to measure impulsive behavior in an animal model of attention deficit hyperactivity disorder (ADHD) of the spontaneously hypertensive rats. Biomol Ther (Seoul) 20:125–131CrossRefGoogle Scholar
- National Research Council (2011) Guide for the care and use of laboratory animals. National Academies Press, Washington, DCGoogle Scholar
- Russell VA (2011) Overview of animal models of attention deficit hyperactivity disorder (ADHD). Curr Protoc Neurosci Chapter 9: Unit9 35Google Scholar
- Sagvolden T, Johansen E (2012) Rat models of ADHD. In: Stanford C, Tannock R (eds) Behavioral neuroscience of attention deficit hyperactivity disorder and its treatment (current topics in behavioral neurosciences). Springer Press, Berlin, pp 301–315Google Scholar
- Sagvolden T, Xu T (2008) l-Amphetamine improves poor sustained attention while d-amphetamine reduces overactivity and impulsiveness as well as improves sustained attention in an animal model of attention-deficit/hyperactivity disorder (ADHD). Behav Brain Funct 4:3PubMedCentralCrossRefPubMedGoogle Scholar
- Scassellati C, Bonvicini C, Faraone SV, Gennarelli M (2012) Biomarkers and attention-deficit/hyperactivity disorder: a systematic review and meta-analyses. J Am Acad Child Adolesc Psychiatr 51(1003–1019), e20Google Scholar
- Umehara M, Ago Y, Kawanai T, Fujita K, Hiramatsu N, Takuma K, Matsuda T (2013b) Methylphenidate and venlafaxine attenuate locomotion in spontaneously hypertensive rats, an animal model of attention-deficit/hyperactivity disorder, through alpha2-adrenoceptor activation. Behav Pharmacol 24:328–331CrossRefPubMedGoogle Scholar