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Published on: November 6, 2018
Nucleus accumbens NMDA receptor subunit expression and function is enhanced in morphine-dependent rats
Fraser Murray1, Neil J Harrison, Sarah Grimwood
1AstraZeneca, Alderley Park, Macclesfiled, Cheshire, SK10 4TG, UK.
Morphine dependence alters N-methyl-d-aspartate (NMDA) receptor expression, decreasing it in some brain areas but increasing it in the nucleus accumbens. This NMDA receptor change enhances function, potentially contributing to opiate dependence.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Previous studies indicated reduced N-methyl-d-aspartate (NMDA) receptor subunits in the forebrain of morphine-dependent rats.
- Morphine dependence is associated with alterations in neurotransmitter systems, including dopamine and glutamate.
Purpose of the Study:
- To investigate regional differences in NMDA receptor expression in morphine-dependent rats.
- To determine the functional relevance of these NMDA receptor changes in the context of opiate dependence.
Main Methods:
- Western blotting was used to quantify NR1, NR2A, and NR2B NMDA receptor subunit protein expression in specific brain regions (frontal cortex, hippocampus, nucleus accumbens).
- MK-801-induced hyperactivity and dopamine metabolism were assessed in morphine-dependent and control rats to evaluate NMDA receptor function.
Main Results:
- NR1 and NR2A NMDA receptor subunits decreased in the frontal cortex and hippocampus but increased significantly in the nucleus accumbens of morphine-dependent rats.
- NR2B subunit expression remained unchanged across all examined brain regions.
- MK-801-induced hyperactivity and dopamine metabolism increases were significantly enhanced in the nucleus accumbens of morphine-dependent rats.
Conclusions:
- NMDA receptor function, particularly involving the NR2A subunit in the nucleus accumbens, is enhanced in morphine-dependent rats.
- This enhanced NMDA receptor function in the nucleus accumbens may play a crucial role in the neurobiological mechanisms underlying opiate dependence.
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