Fig. 2.

Systemically administered metformin increases hippocampal pAMPK and reduces anxiety-like behavior during nicotine withdrawal. (A–C) Western blot analysis of hippocampal AMPK, pAMPK, ACC, and pACC levels at 24 h after nicotine withdrawal in the presence and absence of i.p. metformin (n = 6–7). **P < 0.01; ***P < 0.001. (D) Mice chronically treated with nicotine exhibited a reduced latency to approach a palatable food in a novel environment compared with mice at 24 h after nicotine withdrawal. Metformin reverses the increase in anxiety-like behavior caused by nicotine withdrawal. Bars represent mean latency ± SEM (n = 13–15). *P < 0.05; **P < 0.01. (E) Metformin treatment reduced anxiety-like behavior as measured by the number of marbles buried. Data represent the mean ± SEM number of marbles buried over 15 min (n = 7–16). *P < 0.05.