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Buprenorphine requires concomitant activation of NOP and MOP receptors to reduce cocaine consumption
Author(s) -
Kallupi Marsida,
Shen Qianwei,
Guglielmo Giordano,
Yasuda Dennis,
Journigan V. Blair,
Zaveri Nurulain T.,
Ciccocioppo Roberto
Publication year - 2018
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12513
Subject(s) - buprenorphine , nociceptin receptor , nop , pharmacology , naltrexone , receptor , opioid , chemistry , opioid receptor , medicine , opioid peptide , biochemistry
Buprenorphine's clinical use is approved for the treatment of heroin addiction; however, evidence supporting its efficacy in cocaine abuse also exists. While for heroin it has been demonstrated that the effect of buprenorphine is mediated by its ability to activate μ‐opioid peptide receptor (MOP) receptors, the mechanism through which it attenuates cocaine intake remains elusive. We explored this mechanism using operant models where rodents were trained to chronically self‐administer cocaine for 2 hours daily. Buprenorphine (0.3, 1.0 and 3.0 mg/kg) given intraperitoneally 90 minutes before access to cocaine significantly and dose dependently reduced its intake. Pre‐treatment with naltrexone or with the selective nociceptin/orphanin FQ peptide (NOP) antagonist SB‐612111 did not prevent buprenorphine‐induced reduction of cocaine intake. However, when naltrexone and SB‐612111 were combined, the effect of buprenorphine on cocaine was completely prevented. To confirm that co‐activation of MOP and NOP receptors is the underlying mechanism through which buprenorphine reduces cocaine intake, three compounds, namely, AT‐034, AT‐201 and AT‐202, with a range of affinity and intrinsic activity profiles for MOP and NOP receptors, but weak ability for kappa‐opioid peptide receptor (KOP) transmission, were tested. Consistent with our hypothesis based on buprenorphine's effects, results demonstrated that AT‐034 and AT‐201, which co‐activate MOP and NOP receptors, reduced cocaine self‐administration like buprenorphine. AT‐202, which selectively stimulates NOP receptors, was not effective. Together, these data demonstrate that for buprenorphine, co‐activation of MOP and NOP receptors is essential to reduce cocaine consumption. These results open new vistas on the treatment of cocaine addiction by developing compounds with mixed MOP/NOP agonist properties.