The long-term goal of this study is to elucidate the role of mu opiate receptors in cocaine addiction using positron emission tomography (PET). Efforts to understand the reinforcement mechanisms of cocaine have recently focused on the role of endogenous opioids and opiate receptors. There is compelling experimental animal data demonstrating that cocaine affects the opiate system; these results are being successfully applied to the treatment of cocaine addicts using the partial opioid agonist, buprenorphine. PET provides, for the first time, the opportunity to measure mu-opiate receptors in human cocaine addicts by the use of the mu- selective ligand, 11C-carfentanil. Preliminary results from this laboratory are promising: mu-opiate receptors in several brain regions are significantly increased in cocaine abusers. Thus, the specific aim of this proposal is: To measure regional brain mu opiate receptors in cocaine abusers using 11C-carfentanil and PET. Hypothesis: Cocaine use is associated with increases in mu opiate receptors in brain reward regions such as amygdala, cingulate cortex and striatum. The proposed research design utilizes the noninvasive nature of PET to compare mu opiate receptors in cocaine addicts during chronic abuse and during abstinence, as well as correlates PET data with objective and subjective measures of cocaine abuse. The medical significance of this proposal is threefold: to further understanding of the mechanisms of cocaine reinforcement, to individualize pharmacotherapy, and to contribute to prognosis for cocaine addicts.
| Minkowski, Carolynne P; Epstein, David; Frost, J James et al. (2012) Differential response to IV carfentanil in chronic cocaine users and healthy controls. Addict Biol 17:149-55 |
| Ghitza, Udi E; Preston, Kenzie L; Epstein, David H et al. (2010) Brain mu-opioid receptor binding predicts treatment outcome in cocaine-abusing outpatients. Biol Psychiatry 68:697-703 |
| Gorelick, David A; Kim, Yu Kyeong; Bencherif, Badreddine et al. (2008) Brain mu-opioid receptor binding: relationship to relapse to cocaine use after monitored abstinence. Psychopharmacology (Berl) 200:475-86 |
| Gorelick, David A; Kim, Yu Kyeong; Bencherif, Badreddine et al. (2005) Imaging brain mu-opioid receptors in abstinent cocaine users: time course and relation to cocaine craving. Biol Psychiatry 57:1573-82 |
| Zubieta, J K; Gorelick, D A; Stauffer, R et al. (1996) Increased mu opioid receptor binding detected by PET in cocaine-dependent men is associated with cocaine craving. Nat Med 2:1225-9 |
