Nociceptin/orphanin FQ peptide (NOP) receptor agonists attenuate
morphine-induced conditioned place preference in rodents. However, it is not known whether NOP agonists have reinforcing properties or can inhibit
mu opioid receptor (MOP)-mediated reinforcement as measured by
drug self-administration in rodents. Further understanding the behavioral effects of NOP agonists could suggest them as having potential in attenuating reinforcing effects of
opioids. In the first part of the study, reinforcing properties of selective NOP agonist
SCH221510 were determined and compared with the full MOP agonist
remifentanil under fixed-ratio 5 (FR5) and progressive-ratio (PR) schedules of
drug self-administration. In the second part, effects of systemic and intracisternal pretreatment of
SCH221510 were determined and compared with MOP antagonist
naltrexone in attenuating reinforcing effects of
remifentanil and a non-
drug reinforcer (
sucrose pellets).
Remifentanil self-administration (0.3-10 µg/kg/infusion) generated a biphasic dose-response curve, characteristic of drugs with reinforcing properties.
SCH221510 (3-300 µg/kg/infusion)
self-administration resulted in flat dose-response curves and early break-points under the PR, indicative of drugs lacking reinforcing value. Intracisternally, but not systemically, administered
SCH221510 (0.3-3 µg) attenuated
remifentanil self-administration, comparable with systemic
naltrexone (0.03-0.3 mg/kg).
SCH221510 (1-3 µg), unlike
naltrexone (0.03-1 mg/kg), attenuated responding for
sucrose pellets. Both effects of
SCH221510 were reversed by the NOP antagonist
J-113397 (0.3-3 µg). These results suggest that
SCH221510 does not function as a reinforcer in rats, and that it can attenuate the reinforcing value of MOP agonists; therefore, the potential utility of NOP agonists for the treatment of
drug addiction warrants further evaluation.