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Brain Advance Access originally published online on February 14, 2007
Brain 2007 130(4):1009-1016; doi:10.1093/brain/awm012
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© 2007 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Upregulation of opioid receptor binding following spontaneous epileptic seizures

Alexander Hammers1,2, Marie-Claude Asselin3, Rainer Hinz3, Ian Kitchen4, David J. Brooks1, John S. Duncan2 and Matthias J. Koepp1,2

1MRC Clinical Sciences Centre and Division of Neuroscience, Faculty of Medicine, Imperial College, Hammersmith Hospital, 2Hammersmith Imanet, Hammersmith Hospital, London, 3Department of Clinical and Experimental Epilepsy, Institute of Neurology, UCL, London, National Society for Epilepsy MRI Unit, Chalfont St Peter, UK and 4Pharmacology Group, School of Biomedical and Molecular Sciences, University of Surrey, Guildford, UK

Correspondence to: Dr Matthias Koepp, MD, PhD, Senior Lecturer in Epilepsy, Department of Clinical and Experimental Epilepsy, Institute of Neurology (ION), University College London and National Hospital for Neurology and Neurosurgery (NHNN). Consultant Neurologist, National Society for Epilepsy (NSE), Queen Square, London WC1N 3BG E-mail: mkoepp{at}ion.ucl.ac.uk

Animal and limited human data suggest an important anticonvulsant role for opioid peptides and their receptors. We aimed to provide direct human in vivo evidence for changes in opioid receptor availability following spontaneous seizures. We scanned nine patients within hours of spontaneous temporal lobe seizures and compared their postictal binding of the non-subtype selective opioid receptor PET radioligand [11C]diprenorphine (DPN), quantified as a volume-of-distribution (VD), with interictal binding and with binding changes in 14 healthy controls, controlling for a range of behavioural variables associated with opioid action. A regionally specific increase of opioid receptor availability was evident in the temporal pole and fusiform gyrus ipsilateral to the seizure focus following seizures (Z 5.01, P < 0.001, 16 432 mm3). Within this region, there was a negative correlation between VD and log10 time since last seizure (r = –0.53, P < 0.03), compatible with an early increase and gradual return to baseline. [11C]DPN VD did not undergo systematic changes between time points in controls. This study provides direct human in vivo evidence for changes in opioid receptor availability over a time course of hours following spontaneous seizures, emphasizing an important role of the opioid system in seizure control.

Key Words: temporal lobe epilepsy; opioids; neurotransmission; anterior temporal lobe; positron emission tomography

Abbreviations: DOP, {delta} opioid peptide; DPN, diprenorphine; KOP, {kappa} opioid peptide; MOP, µ opioid peptide; TLE, temporal lobe epilepsy

Received October 3, 2006. Revised January 8, 2007. Accepted January 15, 2007.


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