Prefrontal cortex AMPA receptor plasticity is crucial for cue-induced relapse to heroin-seeking

M.C. van den Oever, N.A. Goriounova, K.W. Li, R.C. van der Schors, R. Binnekade, A.N.M. Schoffelmeer, H.D. Mansvelder, S. Spijker, A.B. Smit, T.J. de Vries

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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. © 2008 Nature Publishing Group.
Original languageEnglish
Pages (from-to)1053-1058
JournalNature neuroscience
Volume11
DOIs
Publication statusPublished - 2008

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