Learning/memory and drug dependence.

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  • NODA Yukihiro
    Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine
  • NABESHIMA Toshitaka
    Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine

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  • 遺伝子変異マウスを用いた薬理学的研究　　学習・記憶と薬物依存
  • 学習・記憶と薬物依存
  • ガクシュウ キオク ト ヤクブツ イゾン

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We investigated the possible mechanisms of development of latent learning and morphine dependence by the methods of behavioral pharmacology and confirmed them by using mutant mice. The heterozygous mice for the tyrosine hydroxylase (TH) gene and for the cyclic AMP (cAMP) response element binding protein (CREB) binding protein (CBP) gene showed the impairment of latent learning in the water finding task, and these mice did not develop morphine dependence. The spatial learning and hippocampal long-term potentiation (LTP) were normal in the both mutants. TH heterozygous mice showed a reduction of high K+-evoked noradrenaline release in the frontal cortex measured by the microdialysis technique and of cAMP content in the brain. In conclusion, the results of mutant mice suggest that the alternation of catecholamine biosynthesis and cAMP signal pathways may play a key role in development of latent learning and morphine dependence, and they furthermore show that the expression of genes mediated by phosphorylated CREB may be involved in the development of latent learning and morphine dependence.<br>

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