Dopamine D1 receptors regulate protein synthesis-dependent long-term recognition memory via extracellular signal-regulated kinase 1/2 in the prefrontal cortex

Taku Nagai, Kazuhiro Takuma, Hiroyuki Kamei, Yukio Ito, Noritaka Nakamichi, Daisuke Ibi, Yutaka Nakanishi, Masaaki Murai, Hiroyuki Mizoguchi, Toshitaka Nabeshima, Kiyofumi Yamada

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137 Citations (Scopus)

Abstract

Several lines of evidence suggest that extracellular signal-regulated kinase1/2 (ERK1/2) and dopaminergic system is involved in learning and memory. However, it remains to be determined if the dopaminergic system and ERK1/2 pathway contribute to cognitive function in the prefrontal cortex (PFC). The amount of phosphorylated ERK1/2 was increased in the PFC immediately after exposure to novel objects in the training session of the novel object recognition test. An inhibitor of ERK kinase impaired long-term recognition memory 24 h after the training although short-term memory tested 1 h after the training was not affected by the treatment. The dopamine D1 receptor agonist increased ERK1/2 phosphorylation in the PFC in vivo as well as in cortical neurons in vitro. Microinjection of the dopamine D1 receptor antagonist into the PFC impaired long-term recognition memory whereas the D2 receptor antagonist had no effect. Immunohistochemistry revealed that exposure to novel objects resulted in an increase in c-Fos expression in the PFC. Microinjection of the protein synthesis inhibitor anisomycin into the PFC impaired the long-term recognition memory. These results suggest that the activation of ERK1/2 following the stimulation of dopamine D1 receptors is necessary for the protein synthesis-dependent long-term retention of recognition memory in the PFC.

Original languageEnglish
Pages (from-to)117-125
Number of pages9
JournalLearning and Memory
Volume14
Issue number3
DOIs
Publication statusPublished - 01-03-2007

All Science Journal Classification (ASJC) codes

  • Neuropsychology and Physiological Psychology
  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

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    Nagai, T., Takuma, K., Kamei, H., Ito, Y., Nakamichi, N., Ibi, D., Nakanishi, Y., Murai, M., Mizoguchi, H., Nabeshima, T., & Yamada, K. (2007). Dopamine D1 receptors regulate protein synthesis-dependent long-term recognition memory via extracellular signal-regulated kinase 1/2 in the prefrontal cortex. Learning and Memory, 14(3), 117-125. https://doi.org/10.1101/lm.461407