Animal models to guide clinical drug development in ADHD: lost in translation?
Version of Record online: 26 SEP 2011
© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society
British Journal of Pharmacology
Special Issue: Themed Issue: Translational Neuropharmacology - Using Appropriate Animal Models to Guide Clinical Drug Development. Guest Editor: A Richard Green
Volume 164, Issue 4, pages 1107–1128, October 2011
How to Cite
Wickens, J. R., Hyland, B. I. and Tripp, G. (2011), Animal models to guide clinical drug development in ADHD: lost in translation?. British Journal of Pharmacology, 164: 1107–1128. doi: 10.1111/j.1476-5381.2011.01412.x
- Issue online: 26 SEP 2011
- Version of Record online: 26 SEP 2011
- Accepted manuscript online: 12 APR 2011 05:04AM EST
- Received; 30 January 2011; Revised; 27 March 2011; Accepted; 29 March 2011
- animal model
We review strategies for developing animal models for examining and selecting compounds with potential therapeutic benefit in attention-deficit hyperactivity disorder (ADHD). ADHD is a behavioural disorder of unknown aetiology and pathophysiology. Current understanding suggests that genetic factors play an important role in the aetiology of ADHD. The involvement of dopaminergic and noradrenergic systems in the pathophysiology of ADHD is probable. We review the clinical features of ADHD including inattention, hyperactivity and impulsivity and how these are operationalized for laboratory study. Measures of temporal discounting (but not premature responding) appear to predict known drug effects well (treatment validity). Open-field measures of overactivity commonly used do not have treatment validity in human populations. A number of animal models have been proposed that simulate the symptoms of ADHD. The most commonly used are the spontaneously hypertensive rat (SHR) and the 6-hydroxydopamine-lesioned (6-OHDA) animals. To date, however, the SHR lacks treatment validity, and the effects of drugs on symptoms of impulsivity and inattention have not been studied extensively in 6-OHDA-lesioned animals. At the present stage of development, there are no in vivo models of proven effectiveness for examining and selecting compounds with potential therapeutic benefit in ADHD. However, temporal discounting is an emerging theme in theories of ADHD, and there is good evidence of increased value of delayed reward following treatment with stimulant drugs. Therefore, operant behaviour paradigms that measure the effects of drugs in situations of delayed reinforcement, whether in normal rats or selected models, show promise for the future.
LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-4