Prefrontal cortex AMPA receptor plasticity is crucial for cue-induced relapse to heroin-seeking.
paper
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- Authors
- Van den Oever, Michel C; Goriounova, Natalia A; Li, Ka Wan; Van der Schors, Roel C; Binnekade, Rob; Schoffelmeer, Anton N M; Mansvelder, Huibert D; Smit, August B; Spijker, Sabine; De Vries, Taco J
- Year
- 2008
- Journal
- Nature neuroscience
- PMID
- 19160503
- DOI
- 10.1038/nn.2165
Associative learning processes have an important role in the initiation and persistence of heroin-seeking. Here we show in a rat self-administration model that reexposure to cues previously associated with heroin results in downregulation of AMPA receptor subunit GluR2 and concomitant upregulation of clathrin-coat assembly protein AP2ml in synaptic membranes of the medial prefrontal cortex (mPFC). Reduced AMPA receptor expression in synaptic membranes was associated with a decreased AMPA/NMDA current ratio and increased rectification index in mPFC pyramidal neurons. Systemic or ventral (but not dorsal) mPFC injections of a peptide inhibiting GluR2 endocytosis attenuated both the rectification index and cue-induced relapse to heroin-seeking, without affecting sucrose-seeking. We conclude that GluR2 receptor endocytosis and the resulting synaptic depression in ventral mPFC are crucial for cue-induced relapse to heroin-seeking. As reexposure to conditioned stimuli is a major cause for heroin relapse, inhibition of GluR2 endocytosis may provide a new target for the treatment of heroin addiction.
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| Title | Year | PMID |
|---|---|---|
| Evidence of CNIH3 involvement in opioid dependence. | 2016 | 26239289 |
| Drug-evoked synaptic plasticity in addiction: from molecular changes to circuit remodeling. | 2011 | 21338877 |
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