Metabolic profiling of the hippocampus of rats experiencing nicotine-withdrawal symptoms

Hayato Akimoto, Shinji Oshima, Yuichi Michiyama, Akio Negishi, Tadashi Nemoto, Daisuke Kobayashi

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Nicotine-withdrawal symptoms have been indicated as a possible risk factor for neuropsychiatric events, such as depression and suicide, during use of smoking-cessation drugs. We aimed to investigate whether the results of the metabolomic analysis of the rat brain reflect nicotine-withdrawal symptoms. We also aimed to investigate the relative changes in each metabolite in the brains of rats with nicotine-withdrawal symptoms. We created rats experiencing nicotine-withdrawal symptoms through repeat administration of nicotine followed by a 12-h withdrawal period, and rats recovered from nicotine-withdrawal symptoms followed by an 18-h withdrawal period. We then implemented brain metabolic profiling by combining high-resolution magic-angle spinning 1 H-NMR spectroscopy with partial least square discriminant analysis (PLS-DA). We found that metabolic profiling of the brain reflects the state during nicotine-withdrawal symptoms and the state after recovery from nicotine-withdrawal symptoms. Additionally, N-acetylaspartate and glutamate increased and aspartate, γ-aminobutyric acid (GABA), and creatine decreased in the hippocampus of rats experiencing nicotine-withdrawal symptoms. Therefore, it is suggested that neurogenesis and neuronal differentiation could be changed and abnormal energy metabolism could occur in the hippocampus during nicotine-withdrawal symptoms.

Original languageEnglish
Pages (from-to)1879-1884
Number of pages6
JournalBiological and Pharmaceutical Bulletin
Issue number12
Publication statusPublished - 2018
Externally publishedYes


  • Hippocampus
  • Metabolomics
  • N-acetylaspartate
  • NMR spectroscopy
  • Nicotine-withdrawal


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