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- Title
Prefrontal cortex AMPA receptor plasticity is crucial for cue-induced relapse to heroin-seeking.
- Authors
Van den Oever, Michel C.; Goriounova, Natalia A.; Ka Wan Li; Van der Schors, Roel C.; Binnekade, Rob; Schoffelmeer, Anton N. M.; Mansvelder, Huibert D.; Smit, August B.; Spijker, Sabine; De Vries, Taco J.
- Abstract
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 AP2m1 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.
- Subjects
LEARNING; HEROIN; HEROIN abuse; NERVOUS system; DRUG administration; PSYCHOLOGY
- Publication
Nature Neuroscience, 2008, Vol 11, Issue 9, p1053
- ISSN
1097-6256
- Publication type
Article
- DOI
10.1038/nn.2165