Figure 1: Knockdown of β3 Integrin, but not β1 Integrin, blocked cue-induced cocaine seeking.
(A) Treatment protocol for morpholino experiments to assess the efficacy of morpholino-knockdown of β3 or β1 Integrin. (B) Scr or β integrin morpholino were microinjected into opposite hemispheres permitting within animal comparison. After β3 morpholino treatment, β3 subunit expression was reduced (paired Student’s t-test t(5)=8.91, p<0.001) without changing the β1 subunit or ILK. After β1 morpholino treatment, the β1 subunit expression was reduced (t-test t(5)=5.75, p<0.01), but β3 subunit (t(5)=3.98, p=0.050) and ILK (t(5)=4.24, p=0.008) expression were elevated. (C) Representative Western blots of each protein and the respective calnexin or GADPH loading control are shown below each bar. Note that because of the relatively weak β3 integrin antibody, a fluorescent secondary was used to augment detection after β1 morpholino treatment. *p<0.05. (D) Diagram of the experimental time line for drug self-administration. (E) Time course of active and inactive lever pressing for self-administration and extinction in cocaine-treated rats used in Figure 1 was equivalent between treatment groups. (F) Cue-induced reinstatement of cocaine seeking was reduced after knockdown of β3 subunit compared to Scr morpholino and potentiated after β1 Integrin knockdown (2-way repeated measures ANOVA, EXT/RST F(1,22)=20.05, p<0.001; Scr/β3/β1 F(2,22)=8.63, p=0.002, interaction F(2,22)=4.78, p=0.019). All data are shown as mean ± SEM, and N is shown within the bars.
*p< 0.05, compared to Scr or Scr/RST, using a Bonferroni’s post hoc test
+p< 0.05, compared to EXT responding within each treatment group