Buprenorphine requires concomitant activation of NOP and MOP receptors to reduce cocaine consumption.
Addict Biol
; 23(2): 585-595, 2018 03.
Article
in En
| MEDLINE
| ID: mdl-28635181
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Behavior, Animal
/
Buprenorphine
/
Cocaine
/
Receptors, Opioid
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Receptors, Opioid, mu
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Dopamine Uptake Inhibitors
/
Narcotic Antagonists
Limits:
Animals
Language:
En
Journal:
Addict Biol
Journal subject:
TRANSTORNOS RELACIONADOS COM SUBSTANCIAS
Year:
2018
Type:
Article
Affiliation country:
Italy