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Central opioidergic pathways may be implicated in the heightened drug cue\u2010reactivity, 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\u2010related cues and matched neutral images before and 10\u201314 days after an injection of extended\u2010release 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\u2010beta\u2010naltrexol, 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\u2010dependent 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\u2010related cues and of the 6\u2010beta\u2010naltrexol levels as potential biomarkers of XRNTX therapeutic effects in patients with opioid dependence.<\/jats:p>","DOI":"10.1111\/j.1369-1600.2012.00462.x","type":"journal-article","created":{"date-parts":[[2012,7,2]],"date-time":"2012-07-02T16:19:15Z","timestamp":1341245955000},"page":"262-271","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Extended\u2010release naltrexone modulates brain response to drug cues in abstinent heroin\u2010dependent patients"],"prefix":"10.1111","volume":"19","author":[{"given":"Daniel D.","family":"Langleben","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kosha","family":"Ruparel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor","family":"Elman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James W.","family":"Loughead","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elliot L.","family":"Busch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Cornish","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin G.","family":"Lynch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elie S.","family":"Nuwayser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna R.","family":"Childress","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles P.","family":"O'Brien","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,7,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/1073858407299288"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2008.12.014"},{"key":"e_1_2_8_4_1","unstructured":"BIOTEK(2005)Depotrex\u00ae Naltrexone Microcapsules Lot 093 Label and Package Insert. 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