The role of the opioid receptor-like (ORL1) receptor in motor stimulatory and rewarding actions of buprenorphine and morphine.
We have previously shown that the ability of buprenorphine to activate the opioid receptor-like (ORL1) receptor compromises its antinociceptive effect. Furthermore, morphine has been shown to alter the level of orphanin FQ/nociceptin (OFQ/N), the endogenous ligand of the ORL1 receptor, raising the possibility that the endogenous OFQ/N/ORL1 receptor system may be involved in the actions of these opioids. Thus, using mice lacking the ORL1 receptor and their wild-type littermates, the present study assessed the role of the ORL1 receptor in psychomotor stimulant and rewarding actions of buprenorphine and morphine. Morphine (5, 10 mg/kg) dose-dependently increased motor activity and induced conditioned place preference. However, the magnitude of each response was comparable for the mutant mice and their wild-type littermates. In contrast, buprenorphine (1 mg/kg) induced greater motor stimulation in ORL1 receptor knockout mice as compared with their wild-type littermates. Further, single conditioning with buprenorphine (3 mg/kg) induced place preference in mutant mice but not in their wild-type littermates. The results of binding assay showed that buprenorphine concentration-dependently (0-1000 nM) displaced specific binding of [(3)H]-OFQ/N in brain membrane of wild-type mice. Together, the present results suggest that the ability of buprenorphine to interact with the ORL1 receptor modulates its acute motor stimulatory and rewarding effects.
Marquez
P
P
Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, 309 East 2nd Street, Pomona, CA 91766, USA.
Borse
J
J
Nguyen
A T
AT
Hamid
A
A
Lutfy
K
K
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002047:Buprenorphine / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004192:Discrimination, Psychological / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009294:Narcotics / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology; D011957:Receptors, Opioid / Q000172:deficiency / Q000502:physiology*; D012201:Reward; D013997:Time Factors; D000094942:Nociceptin Receptor
D009294:Narcotics; D011957:Receptors, Opioid; D002047:Buprenorphine; D009020:Morphine; D000094942:Nociceptin Receptor; C000722287:Oprl1 protein, mouse