Knockdown of the Arc/Arg3.1 protein in the amygdala inhibited GluR1- and GluR2-containing AMPAR endocytosis induced by CMW. A, B, CMW resulted in reduction of surface GluR1- and GluR2-containing AMPARs. Top panels show representative blots of surface (S) and internalized (I) GluR1- (A) and GluR2-containing AMPARs (B) from amygdalar tissues prepared from rats 0.5 and 1 h after conditioned morphine withdrawal. Bottom panels show quantification of surface/internal GluR1- and GluR2-containing AMPARs levels from Western blot data. Error bars represent mean ± SEM. **p < 0.01, compared with the corresponding saline-treated control group, one-way ANOVA with Newman–Keuls post hoc test. C, D, In vivo knockdown of Arc/Arg3.1 inhibited decreases in surface GluR1- and GluR2-containing AMPARs induced by CMW. Top panels show representative blots of surface and internalized GluR1- (C) and GluR2-containg AMPARs (D) from amygdalar tissues prepared from rats 1 h after conditioned morphine withdrawal. Bottom panels show quantification of the S/I ratios of GluR1- and GluR2-containing AMPARs from Western blot data. Error bars represent mean ± SEM. **p < 0.01, ***p < 0.001, compared with the control shRNA-infected groups, two-tailed Student's t test. Total proteins (S+I, normalized to total protein in the lane) levels of GluR1- and GluR2-containing AMPARs have no changes in all groups.