Nucleus Accumbens Long-Term Depression and the Expression of Behavioral Sensitization
Journal - Science
Drug-dependent neural plasticity related to drug addiction andschizophrenia can be modeled in animals as behavioral sensitization,which is induced by repeated noncontingent or self-administrationof many drugs of abuse. Molecular mechanisms that are criticalfor behavioral sensitization have yet to be specified. Long-termdepression (LTD) of -amino-3-hydroxy-5-methyl-isoxazole-4-propionicacid receptor (AMPAR)–mediated synaptic transmission inthe brain has been proposed as a cellular substrate for learningand 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 inhibitedclathrin-mediated endocytosis or by a GluR2-derived peptidethat blocked regulated AMPAR endocytosis. Systemic or intra-NAcinfusion of the membrane-permeable GluR2 peptide prevented theexpression of amphetamine-induced behavioral sensitization inthe rat.* These authors contributed equally to this work.