Nucleus accumbens long-term depression and the expression of behavioral sensitization - PubMed (original) (raw)
. 2005 Nov 25;310(5752):1340-3.
doi: 10.1126/science.1116894.
Affiliations
- PMID: 16311338
- DOI: 10.1126/science.1116894
Nucleus accumbens long-term depression and the expression of behavioral sensitization
Karen Brebner et al. Science. 2005.
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.
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