Brain mu-opioid receptor binding: Relationship to relapse to cocaine use after monitored abstinence

University of Pittsburgh School of Medicine Department of Radiology Pittsburgh PA USA
Psychopharmacology (Impact Factor: 3.99). 11/2008; 200(4):475-486. DOI: 10.1007/s00213-008-1225-5

ABSTRACT RationaleCocaine users have increased regional brain mu-opioid receptor (mOR) binding which correlates with cocaine craving. The relationship
of mOR binding to relapse is unknown.

ObjectiveTo evaluate regional brain mOR binding as a predictor of relapse to cocaine use is the objective of the study.

Materials and methodsFifteen nontreatment-seeking, adult cocaine users were housed on a closed research ward for 12weeks of monitored abstinence
and then followed for up to 1year after discharge. Regional brain mOR binding was measured after 1 and 12weeks using positron
emission tomography (PET) with [11C]carfentanil (a selective mOR agonist). Time to first cocaine use (lapse) and to first two consecutive days of cocaine use
(relapse) after discharge was based on self-report and urine toxicology.

ResultsA shorter interval before relapse was associated with increased mOR binding in frontal and temporal cortical regions at 1
and 12weeks of abstinence (Ps < 0.001) and with a lesser decrease in binding between 1 and 12weeks (Ps < 0.0008). There were significant positive correlations between mOR binding at 12weeks and percent days of cocaine use
during first month after relapse (Ps < 0.002). In multiple linear regression analysis, mOR binding contributed significantly to the prediction of time to relapse
2 = 0.79, P < 0.001), even after accounting for clinical variables.

ConclusionsIncreased brain mOR binding in frontal and temporal cortical regions is a significant independent predictor of time to relapse
to cocaine use, suggesting an important role for the brain endogenous opioid system in cocaine addiction.

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Available from: David A Gorelick, Aug 30, 2015
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    • "Acute oral amphetamine administration has been shown to induce endogenous opioid release in many brain regions frequently implicated in addiction, including the basal ganglia, frontal cortex areas, thalamus, and striatum (Colasanti et al, 2012; Mick et al, 2014). Further, elevated frontal/temporal cortical μ-opioid receptor binding has been observed in cocaine dependence, the degree of which was shown to positively correlate with self-reported cocaine craving (Gorelick et al, 2005), and relate to relapse following treatment (Ghitza et al, 2010; Gorelick et al, 2008). NTX has been shown to block ethanol-induced β-endorphin and subsequent dopamine release in the nucleus accumbens and provide a blockade of ethanol-induced β-endorphin inhibition of GABAergic inhibitory interneurons in the ventral tegmental area (Johnson, 2008; Zalewska-Kaszubska et al, 2006). "
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    • "Interestingly, we have also demonstrated decreased levels of MOPr binding following cue-but not priming-induced reinstatement of cocaine seeking in AcbC and CPu, as well as decreased levels of MOPr binding in cocaine self-administration compared with priming-induced reinstatement in CPu and VDB. Given the positive correlation between MOPr levels with relapse potential of cocaine use in former cocaine addicts (Gorelick et al. 2008), it is possible that the difference in MOPr levels observed in mice subjected to cue-and priming-induced reinstatement of cocaine seeking may at least partly underlie the differences in the magnitude of reinstatement responses induced by the light cue and the priming injection of cocaine observed in our study. Of particular interest was our finding in the BLA, where decreased levels of MOPr binding were observed following cocaine extinction compared with cocaine selfadministration . "
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    Addiction Biology 12/2014; DOI:10.1111/adb.12208 · 5.93 Impact Factor
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    • "opioid receptor agonist ligand [ 11 C ] carfentanil can be almost completely displaced in heroin addicts treated with the partial m receptor agonist , and k / d receptor antagonist buprenorphine ( Green - wald et al . , 2003 ) , and that high cortical binding of [ 11 C ] carfentanil during acute abstinence predicts rapid relapse in cocaine users ( Gorelick et al . , 2008 ) ."
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