Orexin mediates morphine place preference, but not morphine-induced hyperactivity or sensitization.
Orexin (or hypocretin) has been implicated in mediating drug addiction and reward. Here, we investigated orexin's contribution to morphine-induced behavioral sensitization and place preference. Orexin-/- (OKO) mice and littermate wild-type (WT) controls (n=56) and C57BL/6J mice (n=67) were tested for chronic morphine-induced locomotor sensitization or for conditioned place preference (CPP) for a morphine- or a cocaine-paired environment. C57BL/6J mice received the orexin receptor 1 (Ox1r) antagonist, SB-334867, prior to test sessions. OKO mice did not significantly differ from WT controls in locomotor activity following acute- or chronic-morphine treatments. Similarly, mice treated with the Ox1r antagonist did not differ from vehicle controls in locomotor activity following acute- or chronic-morphine treatments. In contrast, while OKO mice did not differ from WT controls in preference for a morphine-paired environment, the Ox1r antagonist significantly attenuated place preference for a morphine-, but not a cocaine-paired, environment. These data suggest that orexin action is not required for locomotor responses to acute and chronic morphine, but Ox1r signaling can influence morphine-seeking in WT animals.
Sharf
Ruth
R
Department of Psychiatry, Ribicoff Research Facilities, Yale University School of Medicine, 34 Park St.-CMHC, New Haven, CT 06519, USA.
Guarnieri
Douglas J
DJ
Taylor
Jane R
JR
DiLeone
Ralph J
RJ
D000818:Animals; D001583:Benzoxazoles / Q000008:administration & dosage / Q000494:pharmacology; D002491:Central Nervous System Agents / Q000008:administration & dosage / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects* / Q000502:physiology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009154:Mutation; D009287:Naphthyridines; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology*; D009479:Neuropeptides / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors / Q000378:metabolism; D013028:Space Perception / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D014508:Urea / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology
C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; D002491:Central Nervous System Agents; D018765:Dopamine Uptake Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D009287:Naphthyridines; D009294:Narcotics; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D009020:Morphine; D014508:Urea; D003042:Cocaine