title: AMPA receptor endocytosis in the amygdala is involved in the disrupted reconsolidation of Methamphetamine-associated contextual memory.
abstract: Repetitive drug taking induces neural long-lasting changes and results in compulsive drug-seeking behavior which may arise from enduring drug memory that impairs cognitive control of motivated behavior. Thus, disrupting these memories could reduce drug seeking. Here, we used a conditioned place preference (CPP) procedure in mice to examine the role of AMPA receptor endocytosis in the basolateral amygdala (BLA) in the disrupted reconsolidation of Methamphetamine (MeAM) memory. Conditioning MeAM (2mg/kg, i.p.) for 3 days in mice markedly increased the time spent in the MeAM-paired compartment tested 24 h after the last injection (CPP test), indicating that MeAM induced a significant rewarding effect. Mice then received anisomycin or vehicle within 1h after CPP test and CPP was re-assessed 24h after CPP test. Mice injected with vehicle exhibited CPP for the previously MeAM-paired chamber whereas mice injected with anisomycin did not. Anisomycin had no effect on the CPP when CPP test was omitted. In addition, anisomycin treatment prevented MeAM priming-induced reinstatement of CPP suggesting the disruption of MeAM memory reconsolidation. MeAM CPP increased surface expression of GluR1 and GluR2 subunits of AMPA receptor in the BLA. Bilateral injection of Tat-GluR23Y, a synthetic peptide that blocked AMPA receptor endocytosis, prevented disruption of MeAM memory reconsolidation. These results suggest that AMPA receptor endocytosis in the BLA is critical for the anisomycin-mediated disruption of reconsolidation of MeAM reward memory.
authors.affiliation: Institute of Basic Medical Sciences and Department of Pharmacology, National Cheng-Kung University, Tainan 701, Taiwan.
authors.forename: Yang-Jung
authors.initials: YJ
authors.lastname: Yu
authors.forename: Chih-Hua
authors.initials: CH
authors.lastname: Chang
authors.forename: Po-Wu
authors.initials: PW
authors.lastname: Gean
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D001245:Association Learning / Q000187:drug effects* / Q000502:physiology; D003216:Conditioning, Operant / Q000187:drug effects; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D058999:Drug-Seeking Behavior / Q000187:drug effects / Q000502:physiology; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D018091:Receptors, AMPA / Q000378:metabolism*
chemical_list: D018765:Dopamine Uptake Inhibitors; D011500:Protein Synthesis Inhibitors; D018091:Receptors, AMPA; D008694:Methamphetamine; D000841:Anisomycin