Abstract
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.
2009 Elsevier B.V. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Benzoxazoles / administration & dosage
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Benzoxazoles / pharmacology
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Central Nervous System Agents / administration & dosage
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Central Nervous System Agents / pharmacology
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Cocaine / administration & dosage
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Cocaine / pharmacology
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Conditioning, Classical / drug effects*
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Conditioning, Classical / physiology
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Dopamine Uptake Inhibitors / administration & dosage
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Dopamine Uptake Inhibitors / pharmacology
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Female
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Intracellular Signaling Peptides and Proteins / deficiency
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Morphine / administration & dosage
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Morphine / pharmacology*
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Motor Activity / drug effects*
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Motor Activity / physiology
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Mutation
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Naphthyridines
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Narcotics / administration & dosage
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Narcotics / pharmacology*
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Neuropeptides / deficiency
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Neuropeptides / genetics
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Neuropeptides / metabolism*
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Orexin Receptors
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Orexins
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Receptors, G-Protein-Coupled / antagonists & inhibitors
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Receptors, G-Protein-Coupled / metabolism
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Receptors, Neuropeptide / antagonists & inhibitors
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Receptors, Neuropeptide / metabolism
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Space Perception / drug effects*
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Space Perception / physiology
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Time Factors
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Urea / administration & dosage
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Urea / analogs & derivatives
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Urea / pharmacology
Substances
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1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea
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Benzoxazoles
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Central Nervous System Agents
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Dopamine Uptake Inhibitors
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Intracellular Signaling Peptides and Proteins
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Naphthyridines
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Narcotics
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Neuropeptides
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Orexin Receptors
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Orexins
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Receptors, G-Protein-Coupled
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Receptors, Neuropeptide
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Morphine
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Urea
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Cocaine