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Science 310 (5752): 1340-1343

Copyright © 2005 by the American Association for the Advancement of Science

Nucleus Accumbens Long-Term Depression and the Expression of Behavioral Sensitization

Karen Brebner,1,3* Tak Pan Wong,1,2* Lidong Liu,1,2 Yitao Liu,1,2 Paul Campsall,1,2 Sarah Gray,1,3 Lindsay Phelps,1,3 Anthony G. Phillips,1,3{dagger} Yu Tian Wang1,2{dagger}

Abstract: Drug-dependent neural plasticity related to drug addiction and schizophrenia can be modeled in animals as behavioral sensitization, which is induced by repeated noncontingent or self-administration of many drugs of abuse. Molecular mechanisms that are critical for behavioral sensitization have yet to be specified. Long-term depression (LTD) of {alpha}-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptor (AMPAR)–mediated synaptic transmission in the brain has been proposed as a cellular substrate for learning and memory. The expression of LTD in the nucleus accumbens (NAc) required clathrin-dependent endocytosis of postsynaptic AMPARs. NAc LTD was blocked by a dynamin-derived peptide that inhibited clathrin-mediated endocytosis or by a GluR2-derived peptide that blocked regulated AMPAR endocytosis. Systemic or intra-NAc infusion of the membrane-permeable GluR2 peptide prevented the expression of amphetamine-induced behavioral sensitization in the rat.

1 Brain Research Centre, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada.
2 Department of Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada.
3 Department of Psychiatry, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: aphillips{at} (A.G.P.); ytwang{at} (Y.T.W.)

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