Orexin mediates morphine place preference, but not morphine-induced hyperactivity or sensitization

Brain Res. 2010 Mar 4;1317:24-32. doi: 10.1016/j.brainres.2009.12.035. Epub 2009 Dec 23.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoxazoles / administration & dosage
  • Benzoxazoles / pharmacology
  • Central Nervous System Agents / administration & dosage
  • Central Nervous System Agents / pharmacology
  • Cocaine / administration & dosage
  • Cocaine / pharmacology
  • Conditioning, Classical / drug effects*
  • Conditioning, Classical / physiology
  • Dopamine Uptake Inhibitors / administration & dosage
  • Dopamine Uptake Inhibitors / pharmacology
  • Female
  • Intracellular Signaling Peptides and Proteins / deficiency
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Morphine / administration & dosage
  • Morphine / pharmacology*
  • Motor Activity / drug effects*
  • Motor Activity / physiology
  • Mutation
  • Naphthyridines
  • Narcotics / administration & dosage
  • Narcotics / pharmacology*
  • Neuropeptides / deficiency
  • Neuropeptides / genetics
  • Neuropeptides / metabolism*
  • Orexin Receptors
  • Orexins
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Neuropeptide / antagonists & inhibitors
  • Receptors, Neuropeptide / metabolism
  • Space Perception / drug effects*
  • Space Perception / physiology
  • Time Factors
  • Urea / administration & dosage
  • Urea / analogs & derivatives
  • Urea / pharmacology

Substances

  • 1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea
  • Benzoxazoles
  • Central Nervous System Agents
  • Dopamine Uptake Inhibitors
  • Intracellular Signaling Peptides and Proteins
  • Naphthyridines
  • Narcotics
  • Neuropeptides
  • Orexin Receptors
  • Orexins
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide
  • Morphine
  • Urea
  • Cocaine