What have positron emission tomography and ‘Zippy’ told us about the neuropharmacology of drug addiction?
Article first published online: 25 JUL 2011
© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society
British Journal of Pharmacology
Special Issue: Themed Section: Imaging - the Interface with Pharmacology. Guest Editors: Andrew Lawrence and Andreas Heinz
Volume 163, Issue 8, pages 1586–1604, August 2011
How to Cite
Cumming, P., Caprioli, D. and Dalley, J. W. (2011), What have positron emission tomography and ‘Zippy’ told us about the neuropharmacology of drug addiction?. British Journal of Pharmacology, 163: 1586–1604. doi: 10.1111/j.1476-5381.2010.01036.x
- Issue published online: 25 JUL 2011
- Article first published online: 25 JUL 2011
- Accepted manuscript online: 15 SEP 2010 05:13AM EST
- Received; 10 June 2010; Revised; 9 August 2010; Accepted; 31 August 2010
- positron emission tomography;
Translational molecular imaging with positron emission tomography (PET) and allied technologies offer unrivalled applications in the discovery of biomarkers and aetiological mechanisms relevant to human disease. Foremost among clinical PET findings during the past two decades of addiction research is the seminal discovery of reduced dopamine D2/3 receptor expression in the striatum of drug addicts, which could indicate a predisposing factor and/or compensatory reaction to the chronic abuse of stimulant drugs. In parallel, recent years have witnessed significant improvements in the performance of small animal tomographs (microPET) and a refinement of animal models of addiction based on clinically relevant diagnostic criteria. This review surveys the utility of PET in the elucidation of neuropharmacological mechanisms underlying drug addiction. It considers the consequences of chronic drug exposure on regional brain metabolism and neurotransmitter function and identifies those areas where further research is needed, especially concerning the implementation of PET tracers targeting neurotransmitter systems other than dopamine, which increasingly have been implicated in the pathophysiology of drug addiction. In addition, this review considers the causal effects of behavioural traits such as impulsivity and novelty/sensation-seeking on the emergence of compulsive drug-taking. Previous research indicates that spontaneously high-impulsive rats – as exemplified by ‘Zippy’– are pre-disposed to escalate intravenous cocaine self-administration, and subsequently to develop compulsive drug taking tendencies that endure despite concurrent adverse consequences of such behaviour, just as in human addiction. The discovery using microPET of pre-existing differences in dopamine D2/3 receptor expression in the striatum of high-impulsive rats suggests a neural endophenotype that may likewise pre-dispose to stimulant addiction in humans.
LINKED ARTICLES This article is part of a themed section on Imaging. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2011.163.issue-8BJP has previously published an Imaging in Pharmacology themed section, edited by A Davenport and C Daly. To view this section visit http://dx.doi.org/10.1111/bph.2010.159.issue-4