Nucleus accumbens long-term depression and the expression of behavioral sensitization.
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.
Brebner
Karen
K
Brain Research Centre, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada.
Wong
Tak Pan
TP
Liu
Lidong
L
Liu
Yitao
Y
Campsall
Paul
P
Gray
Sarah
S
Phelps
Lindsay
L
Phillips
Anthony G
AG
Wang
Yu Tian
YT
D000818:Animals; D016739:Behavior, Addictive; D001522:Behavior, Animal / Q000187:drug effects*; D002478:Cells, Cultured; D002966:Clathrin / Q000502:physiology; D003913:Dextroamphetamine / Q000008:administration & dosage* / Q000494:pharmacology; D034281:Dynamins / Q000494:pharmacology; D004705:Endocytosis; D019706:Excitatory Postsynaptic Potentials; D036881:Long-Term Synaptic Depression / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology
D002966:Clathrin; D010455:Peptides; D018091:Receptors, AMPA; D011993:Recombinant Fusion Proteins; D034281:Dynamins; C104722:glutamate receptor ionotropic, AMPA 2; D003913:Dextroamphetamine