Orphanin FQ/nociceptin but not Ro 65-6570 inhibits the expression of cocaine-induced conditioned place preference

Behav Pharmacol. 2002 May;13(3):229-35. doi: 10.1097/00008877-200205000-00006.


The present study investigated the effect of orphanin FQ/nociceptin (OFQ/N), the endogenous ligand of the opioid receptor-like 1 (ORL-1) receptor on the expression of cocaine-induced conditioned place preference (CPP) in rats. To extend this study, the new non-peptidic compound Ro 65-6570 (8-acenaphthen-1-yl-1-phenyl-1,3,8-triaza-spiro[4,5]decan-4-one), with agonist activity at ORL-1 receptors, was examined. The influence of both compounds on cocaine-induced hyperactivity was also studied. Our experiments indicated that intracerebroventricular (i.c.v.) injection of OFQ/N, at doses of 10 and 20 microg/rat, significantly suppressed the expression of cocaine-induced place preference. Ro 65-6570 (3 and 6 mg/kg, i.p.) did not change the effect of cocaine, although its acute injection in control rats significantly increased the time spent in the drug-associated compartment of the CPP apparatus. The substances exhibited opposite effects on cocaine-induced hyperactivity (OFQ/N suppressed it but Ro 65-6570 increased it). Our results suggest that the effect of OFQ/N on the expression of cocaine-induced CPP may be a result of its influence on dopamine (DA) neurotransmission in mesolimbic structures. Ro 65-6570 does not share this effect with OFQ/N.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cocaine / antagonists & inhibitors*
  • Cocaine / pharmacology*
  • Conditioning, Operant / drug effects*
  • Imidazoles / pharmacology*
  • Injections, Intraventricular
  • Ligands
  • Male
  • Motor Activity / drug effects
  • Opioid Peptides / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, Opioid / drug effects
  • Spiro Compounds / pharmacology*


  • 8-acenaphthen-1-yl-1-phenyl-1,3,8-triazaspiro(4.5)decan-4-one
  • Imidazoles
  • Ligands
  • Opioid Peptides
  • Receptors, Opioid
  • Spiro Compounds
  • nociceptin
  • nociceptin receptor
  • Cocaine