Fig. 3: Modulation of AMPK activity by adenovirus gene transfer in the NAcsh controls cocaine reinforcement and motivation.
From: Novel role of AMPK in cocaine reinforcement via regulating CRTC1
A Timeline of the experiment. The rats received intra-NAcsh infusions of Ad-GFP, Ad-constitutively active (CA)-AMPK, or Ad-dominant negative (DN)-AMPK. The rats were then trained to self-administer intravenous injections of cocaine under an FR1 schedule in daily 3 h sessions. The response requirement was gradually increased to FR5, and training continued until cocaine intake stabilized. The rats then underwent a between-session dose-response test and progressive-ratio test. B Photomicrographs of Ad-GFP injection sites in the NAcsh (scale bar = 200 μm [left], 50 μm [right]). C–E Infusions (C), active nosepokes (D), and inactive nosepokes (E) during daily 3 h self-administration sessions. F Increasing or decreasing AMPK activity by adenovirus expressing CA-AMPK or DN-AMPK in the NAcsh produced opposite changes in cocaine self-administration dose-response curves (n = 9–11/group). G Animals that received adenovirus-expressing DN-AMPK subsequently achieved a higher ratio of lever-press responses per cocaine injection before ceasing self-administration in a progressive-ratio test at the 0.75 mg/kg dose of cocaine (n = 8–11/group). The data are expressed as mean ± SEM. Post hoc analyses were performed using the Tukey test. *p < 0.05, **p < 0.01, compared with Ad-GFP group.
