title: Extended-release naltrexone modulates brain response to drug cues in abstinent heroin-dependent patients.
abstract: Drug cues play an important role in relapse to drug use. Naltrexone is an opioid antagonist that is used to prevent relapse in opioid dependence. Central opioidergic pathways may be implicated in the heightened drug cue-reactivity, but the effects of the opioid receptors' blockade on the brain responses to drug cues in opioid dependence are unknown. To pursue this question, we studied 17 abstinent i.v. heroin users with brain functional magnetic resonance imaging (fMRI) during exposure to visual heroin-related cues and matched neutral images before and 10-14 days after an injection of extended-release naltrexone (XRNTX). Whole brain analysis of variance of fMRI data showed main effect of XRNTX in the medial frontal gyrus, precentral gyrus, cuneus, precuneus, caudate and the amygdala. fMRI response was decreased in the amygdala, cuneus, caudate and the precentral gyrus and increased in the medial frontal gyrus and the precuneus. Higher plasma levels of naltrexone's major metabolite, 6-beta-naltrexol, were associated with larger reduction in the fMRI response to drug cues after XRNTX in the precentral, caudate and amygdala clusters. The present data suggest that XRNTX pharmacotherapy of opioid-dependent patients may, respectively, decrease and potentiate prefrontal and limbic cortical responses to drug cues and that this effect might be related to the XRNTX metabolism. Our findings call for further evaluation of the brain fMRI response to drug-related cues and of the 6-beta-naltrexol levels as potential biomarkers of XRNTX therapeutic effects in patients with opioid dependence.
authors: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA Veterans Administration Health Care System, Philadelphia, PA, USA Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
authors: Daniel D
authors: DD
authors: Langleben
authors: Kosha
authors: K
authors: Ruparel
authors: Igor
authors: I
authors: Elman
authors: James W
authors: JW
authors: Loughead
authors: Elliot L
authors: EL
authors: Busch
authors: James
authors: J
authors: Cornish
authors: Kevin G
authors: KG
authors: Lynch
authors: Elie S
authors: ES
authors: Nuwayser
authors: Anna R
authors: AR
authors: Childress
authors: Charles P
authors: CP
authors: O'Brien
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D003463:Cues; D003692:Delayed-Action Preparations / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006556:Heroin Dependence / Q000503:physiopathology* / Q000534:rehabilitation; D006801:Humans; D016014:Linear Models; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D010100:Oxygen / Q000097:blood; D010775:Photic Stimulation / Q000379:methods; D055502:Secondary Prevention
chemical_list: D003692:Delayed-Action Preparations; D009292:Narcotic Antagonists; C010410:6 beta-hydroxynaltrexone; D009271:Naltrexone; D010100:Oxygen