Examining the reinforcing properties of NOP receptor agonist SCH221510 and its role in attenuating mu‐receptor mediated reinforcement in a rat self‐administration assay

Abstract

Nociceptin/orphanin FQ receptor (NOP) plays a critical role in regulation of reward and motivation neuropathways. In rodents, NOP agonists do not produce conditioned place preference and block rewarding effects of opiates and psychostimulants. We used a rat self‐administration assay to determine reinforcing properties of NOP agonist SCH221510 and its role in attenuating reinforcing effects of mu‐opioid receptor (MOP) agonist remifentanil. Rats with intravenous catheters were allowed to self‐administer SCH221510 (3–300 μg/kg/infusion) or remifentanil (0.3–10 μg/kg/infusion) under fixed (FR5) and progressive ratio (PR) schedules of reinforcement. All rats self‐administered remifentanil, generating a biphasic dose effect curve typical of intravenous drug self‐administration. SCH221510 did not maintain responding, resulting in a flat dose effect curve. Under PR, break points for SCH221510 were similar to those of vehicle, whereas remifentanil had significantly higher break points. Intracisternal (0.03–3 μg) but not systemic (1–10 mg/kg, s.c.) administration of SCH221510 decreased responding for remifentanil (3.2 μg/kg/infusion). This effect was comparable to that of MOP antagonist naltrexone (0.03– 0.3 mg/kg s.c.). Hence, our data show that NOP agonists do not function as reinforcers and may block reinforcing effects of MOP agonists (Supported by USPHS grant R01‐DA032568).