Abstract
The nociceptin/orphanin FQ peptide (NOP) receptor, the fourth opioid receptor subtype, mediates distinctive actions in monkeys that suggest a possibility that NOP agonists may result in strong analgesia in the absence of side effects that are found in mu opioid receptor (MOP) agonists in primates. The aim of this study was to investigate and compare the behavioral effects of NOP agonists, Ro 64‐6198 and SCH221510, in side‐by‐side comparisons with MOP agonists, morphine and alfentanil, in rhesus monkeys. Both NOP and MOP agonists dose‐dependently produced antinociceptive effects against a noxious stimulus. Antagonist studies demonstrated that NOP and MOP receptors independently mediate antinociceptive actions. However, at antinociceptive doses, MOP agonists, but not NOP agonists, produced respiratory depression. NOP agonists did not produce reinforcing effects comparable with those of MOP agonists under the self‐administration procedure. In addition, at equianalgesic doses, injections of 3 mg/kg of morphine, but not 0.01 mg/kg of SCH221510, significantly delayed the gastrointestinal transit rate of monkeys, indicating that NOP agonists lack of constipating effects of MOP agonists. These results suggest that activation of NOP receptors produces antinociception with reduced abuse liability and fewer side effects in primates (Supported by USPHS grant AR‐059193).
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