Figure 11.

Viral knockdown of GluN2B in NAc core does not influence incubation of cocaine craving during withdrawal. A, GluN2B knockdown before cocaine self-administration did not impact drug taking during the training period. Mixed-effect analysis: self-administration day, F_(9,155) = 4.476 p < 0.0001; active versus control virus, F_(1,18) = 0.02696, NS; interaction (self-administration day vs active/control virus), F_(9,155) = 1.568, NS. Post hoc tests were not significant (Holm–Sidak). B, GluN2B knockdown did not prevent incubation of craving, measured as increased cue-induced responding in the previously active nose-poke hole on WD49 versus WD1. A three-way repeated-measures ANOVA (nose-poke hole × virus condition × WD) revealed a main effect of WD (F_(1,36) = 9.477, p = 0.004) but no significant WD × virus condition interaction (F_(1,36) = 0.1709, NS). In both control and active siRNA groups, there was a significant increase in nose-pokes from WD1 to WD49 (Bonferroni-corrected planned comparisons: control WD1 vs WD49, p = 0.0168; siRNA WD1 vs WD49, p = 0.0003). C, Viral efficacy indicated by decreased GluN2B protein expression in NAc core of drug-naive rats. Upper bands represent GluN2B, and lower bands represent a prominent Ponceau S-stained band from the same lane; Ponceau staining in the entire lane was our measure of protein loading. Unpaired t test: control versus GluN2B siRNA (t₍₁₂₎ = 4.02, p < 0.001). D, Visualization of virus expression based on GFP fluorescence in NAc core of a representative drug-naive rat. Scale bar, 50 µm. **p < 0.01, ***p < 0.001.