Article abstract
Nature Neuroscience 11, 1053 - 1058 (2008)
Published online: 1 August 2008 | doi:10.1038/nn.2165
Prefrontal cortex AMPA receptor plasticity is crucial for cue-induced relapse to heroin-seeking
Michel C Van den Oever1, Natalia A Goriounova2, Ka Wan Li1, Roel C Van der Schors1, Rob Binnekade3, Anton N M Schoffelmeer3, Huibert D Mansvelder2, August B Smit1, Sabine Spijker1,4 & Taco J De Vries1,3,4
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.
- Departments of Molecular and Cellular Neurobiology, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands.
- Integrative Neurophysiology, Center for Neurogenomics & Cognitive Research, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands.
- Anatomy and Neurosciences, Center for Neurogenomics & Cognitive Research, VU Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
- These authors contributed equally to this work.
Correspondence to: Sabine Spijker1,4 e-mail: sabine.spijker@cncr.vu.nl
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