Orphanin FQ/nociceptin but not Ro 65-6570 inhibits the expression of cocaine-induced conditioned place preference.
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.
Department of Pharmacodynamics, Medical Academy, 20-081 Lublin, Poland. jolka@panaceum.am.lubin.pl
J
J
Kotlińska
J
J
Wichmann
A
A
Legowska
K
K
Rolka
J
J
Silberring
D000818:Animals; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008024:Ligands; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018847:Opioid Peptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000187:drug effects; D013141:Spiro Compounds / Q000494:pharmacology*; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D003042:Cocaine; D007093:Imidazoles; D008024:Ligands; D018847:Opioid Peptides; D011957:Receptors, Opioid; D013141:Spiro Compounds; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C121726:8-acenaphthen-1-yl-1-phenyl-1,3,8-triazaspiro(4.5)decan-4-one; C000722285:Oprl1 protein, rat