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Morphine causes a delayed increase in glutamate receptor functioning in the nucleus accumbens core
Edwin H Jacobs1, George Wardeh, August B Smit
1Research Institute Neurosciences Vrije Universiteit, Drug Abuse Program, Department of Medical Pharmacology, Free University Medical Center, VUmc, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
European Journal of Pharmacology
|March 22, 2005
Summary
Morphine addiction may be prolonged by increased glutamate signaling in the brain. This study shows morphine enhances glutamate receptor function and gene expression in rat nucleus accumbens over time, contributing to addiction persistence.
Area of Science:
- Neuroscience
- Addiction Research
- Neuropharmacology
Background:
- Enhanced excitatory neurotransmission in the mesocorticolimbic system is implicated in addiction.
- Understanding the temporal dynamics of neurotransmitter system changes post-drug exposure is crucial.
Purpose of the Study:
- To investigate the effect of a single morphine injection on glutamate-induced gamma-aminobutyric acid (GABA) release in the rat nucleus accumbens core.
- To determine the association between morphine exposure and the expression of glutamate receptor subunits.
Main Methods:
- Superfused rat nucleus accumbens core slices were used to measure [3H]-gamma-aminobutyric acid (GABA) release.
- Glutamate, N-methyl-D-aspartate (NMDA), and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) were used to stimulate GABA release.
- Gene transcript levels of ionotropic NMDA and AMPA/kainate receptor subunits were analyzed.
Main Results:
- A single subcutaneous morphine injection profoundly enhanced glutamate-, NMDA-, and AMPA-induced GABA release 3 weeks, but not 3 days, post-injection.
- This delayed enhancement in glutamate receptor function correlated with increased gene transcript levels of ionotropic NMDA and AMPA/kainate receptor subunits.
Conclusions:
- Morphine exposure leads to a delayed, progressive enhancement of glutamate neurotransmission in the nucleus accumbens core.
- These findings suggest that alterations in glutamate receptor function and expression contribute to the persistence of addiction behaviors.