To Study the Mechanism of Destabilization of Methamphetamine-related Memory in Amygdala

  • 余 泱蓉

Student thesis: Doctoral Thesis


Repetitive drug taking induces neural long-lasting changes and results in compulsive drug-seeking behavior known as addiction Drug withdrawal is easy to relapse which may result from drug memory Thus recent literatures focus on disrupting these memories to reduce drug seeking Reconsolidation involves retrieval-induced destabilization and restabilization processes in order for memories to be updated Retrieval-induced destabilization render memories susceptible to disruption by amnestic agents Previous studies revealed that the amygdala is involved in the drug memory However the role of the amygdala in the regulation of drug memory reconsolidation and its participation in the mechanisms still need more discussion Here we used conditioned place preference (CPP) procedure in mice to delineate the cellular mechanism underlying the destabilization of drug-related memory in amygdala Methamphetamine conditioning (MeAM) for 3 days in mice (2 mg/kg i p ) induced a significant reward effect Mice then received anisomycin (ANI) within 1 hour after retrieval to disrupt reconsolidation of MeAM-related memory ANI reversed MeAM-induced increase in the level of surface AMPA receptors (AMPARs) phosphorylation of GluR1-Serine845 (p-GluR1-Ser845) dendritic spines and the excitatory synaptic transmission in the basal lateral amygdala (BLA) The effects of ANI were prevented by bilateral injection of synthetic peptide that blocked AMPAR endocytosis N-methyl-D-aspartate receptor (NMDAR) antagonist NR2B-containing NMDAR antagonist calcineurin inhibitors and protein phosphatase 1 inhibitors These results suggest that memory retrieval induces activation of NR2B-containing NMDARs which allows the influx of Ca2+ Increased intracellular Ca2+ stimulates calcineurin leading to dephosphorylation and inactivation of inhibitor 1 and activation of protein phosphatase 1 Protein phosphatase 1 then dephosphorylates p-GluR1-ser845 to elicit AMPAR endocytosis and destabilization of drug-related memory
Date of Award2016 Feb 1
Original languageEnglish
SupervisorPo-Wu Gean (Supervisor)

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