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Related Experiment Videos

Enhanced spinal nociceptin receptor expression develops morphine tolerance and dependence.

H Ueda1, M Inoue, H Takeshima

  • 1Department of Molecular Pharmacology and Neuroscience, Nagasaki University School of Pharmaceutical Sciences, Nagasaki 852-8521, Japan.ueda@net.nagasaki-u.ac.jp.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|October 12, 2000
PubMed
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The anti-opioid nociceptin receptor (NOR) system in the spinal cord contributes to morphine tolerance and dependence. Blocking NOR with a novel antagonist reduced these effects in mice, suggesting a therapeutic target.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Molecular Biology

Background:

  • Chronic morphine use leads to tolerance and dependence, involving neuronal plasticity.
  • The role of the anti-opioid nociceptin receptor (NOR) system in these adaptations is not fully understood.

Purpose of the Study:

  • To investigate if increased NOR system activity underlies opioid tolerance and dependence.
  • To examine the effects of chronic morphine on NOR gene expression.

Main Methods:

  • Utilized nociceptin receptor knock-out (NOR(-/-)) mice and a novel NOR antagonist (J-113397).
  • Assessed morphine analgesic tolerance and physical dependence using behavioral tests (tail-pinch, tail-flick, naloxone-precipitated withdrawal).
  • Measured NOR gene expression in the spinal cord.

Related Experiment Videos

Main Results:

  • NOR(-/-) mice exhibited resistance to morphine tolerance and attenuated physical dependence.
  • J-113397 administration significantly reduced morphine tolerance and dependence.
  • Chronic morphine treatment increased NOR gene expression in the spinal cord.

Conclusions:

  • The spinal NOR system plays a crucial role in developing morphine tolerance and dependence.
  • Targeting the spinal NOR system may offer a strategy to mitigate opioid tolerance and dependence.