Related Experiment Video

Updated: Aug 14, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
07:23

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities

Published on: July 29, 2014

AMPA antagonist LY293558 blocks the development, without blocking the expression, of behavioral sensitization to

W A Carlezon1, K Rasmussen, E J Nestler

  • 1Laboratory of Molecular Psychiatry, Yale University School of Medicine, Connecticut Mental Health Center, New Haven 06508, USA.

Synapse (New York, N.Y.)
|March 2, 1999
PubMed

Insights

The AMPA antagonist LY293558 blocks the development, but not the expression, of morphine-induced locomotor activity sensitization in rats. This highlights the role of AMPA receptors in the initial neuroadaptations to chronic morphine exposure.

Area of Science:

  • Neuropharmacology
  • Behavioral Neuroscience
  • Addiction Research

Background:

  • Morphine, a potent opioid analgesic, stimulates locomotor activity in rats.
  • Repeated morphine administration leads to sensitization, an enhanced response with continued exposure.
  • The neurobiological mechanisms underlying morphine sensitization are not fully understood.

Purpose of the Study:

  • To investigate the role of AMPA receptors in the development and expression of morphine sensitization.
  • To determine the effects of the AMPA antagonist LY293558 on morphine-induced locomotor activity and sensitization.

Main Methods:

  • Rats were treated with morphine (3.0 mg/kg, s.c.) to induce locomotor activity.
  • The AMPA antagonist LY293558 was administered systemically at various doses (0.1-3.0 mg/kg) before morphine.
  • Locomotor activity was measured, and sensitization was assessed after repeated intermittent morphine treatment.

Main Results:

  • High doses of LY293558 (3.0 mg/kg) attenuated acute morphine-induced locomotor stimulation.
  • LY293558 (0.3-3.0 mg/kg) blocked the development of morphine sensitization during repeated treatment.
  • LY293558 did not affect the expression of pre-established morphine sensitization.

Conclusions:

  • AMPA receptors are critically involved in the initiation of neuroadaptations underlying morphine sensitization.
  • LY293558 inhibits the development of morphine tolerance but does not alter its established effects.
  • These findings suggest distinct roles for AMPA receptors in the induction versus expression phases of opioid-induced plasticity.

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