title: Upregulation of opioid receptor binding following spontaneous epileptic seizures.
abstract: 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.
authors.affiliation: MRC Clinical Sciences Centre and Division of Neuroscience, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hammers
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Asselin
authors.forename: Rainer
authors.initials: R
authors.lastname: Hinz
authors.forename: Ian
authors.initials: I
authors.lastname: Kitchen
authors.forename: David J
authors.initials: DJ
authors.lastname: Brooks
authors.forename: John S
authors.initials: JS
authors.lastname: Duncan
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Koepp
mesh_terms: D000328:Adult; D000368:Aged; D004174:Diprenorphine; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods; D011957:Receptors, Opioid / Q000378:metabolism*; D013702:Temporal Lobe / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
chemical_list: D009292:Narcotic Antagonists; D018847:Opioid Peptides; D011957:Receptors, Opioid; D004174:Diprenorphine