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. Author manuscript; available in PMC: 2018 Jun 1.
Published in final edited form as: Biol Psychiatry. 2016 Oct 13;81(11):959–970. doi: 10.1016/j.biopsych.2016.10.005

Figure 5. Repeated MA experience elevates NACs Homer2 expression to promote MA-seeking and – taking.

Figure 5

(A) Immunoblotting conducted on the NACs of B6 mice treated repeatedly with MA (10 IP injections of 2 mg/kg) revealed a moderate, albeit significant, reduction in Homer1b/c expression relative to SAL controls, irrespective of withdrawal [Treatment effect: F(1,36)=4.61, p=0.04; n’s=11–12]. Interestingly, these same animals exhibited a polar opposite increase in Homer2a/b expression [Treatment effect: F(1,31)=5.47, p=0.03; n’s=11–12]. (B) No changes in Homer protein expression were observed within the adjacent NACc (Treatment X Withdrawal ANOVAs, all p’s>0.20; n’s=10–12). For both panels a & b, representative immunoblots are provided, corresponding with their respective datasets above and *p<0.05 denotes a main Treatment effect (p<0.05). (C) When tested in a MA-free state, an intra-NACs infusion of AAV-shRNA-Homer2b did not impact the magnitude of a MA-conditioned place-preference induced by 4 pairings of 2 mg/kg MA. However, only GFP animals exhibited a relative increase in place-preference magnitude when tested in the presence of a 2 mg/kg MA interoceptive cue, however the group difference in this regard was shy of statistical significance [AAV X Side X Test: F(1,23)=3.04, p=0.09]. (D) During operant conditioning for reinforcement by 10 mg/L MA, shRNA-infused mice emitted fewer nose-pokes than green fluorescent protein (GFP) controls with increasing response requirement [AAV X Schedule: F(2,44)=5.92, p=0.005; *p<0.05 vs. GFP, t-tests]. (E) In parallel, shRNA-infused mice consumed less MA with increasing response requirement during this training phase [AAV X Schedule: F(2,44)=7.84, p=0.001; *p<0.05 vs. GFP, t-tests]. (F) shRNA-Homer2b infusion also flattened the MA dose-nose-poke response function under an FR1/FI20 schedule of reinforcement [AAV X Dose: F(4,88)=4.75, p=0.002; *p<0.05 vs. GFP, t-tests]. (G) Although it appeared that shRNA-Homer2b infusion reduced the intake of 10 mg/L MA, there was no systematic effect of knock-down on the MA dose-intake function [AAV X Dose, p>0.3]. (H) Visualization of the GFP reporter by fluorescent microscopy indicating neuronal transduction within the NACs at 10X magnification. For panels c–g, sample sizes are indicated in parentheses.