Repeated methamphetamine treatment impairs recognition memory through a failure of novelty-induced ERK1/2 activation in the prefrontal cortex of mice

Hiroyuki Kamei, Taku Nagai, Hiroko Nakano, Yuriko Togan, Masanori Takayanagi, Kenji Takahashi, Kana Kobayashi, Shigeru Yoshida, Kenji Maeda, Kazuhiro Takuma, Toshitaka Nabeshima, Kiyofumi Yamada

Research output: Contribution to journalArticlepeer-review

126 Citations (Scopus)

Abstract

Background: Recent clinical studies have suggested that chronic use of methamphetamine (METH) induces long-term cognitive deficits. To clarify the mechanism of METH-induced cognitive impairment, we investigated the effect of METH on cognitive function in mice. Methods: Mice were repeatedly administered METH for 7 days, and their cognitive function was assessed using a novel-object recognition task. Therapeutic effects of clozapine and haloperidol on METH-induced cognitive impairment were investigated. Western blotting and specific inhibitors were employed to determine the role of extracellular signal-regulated kinase 1/2 (ERK1/2). Results: Repeated METH treatment induced an impairment of recognition of novel objects and behavioral sensitization. These effects persisted for at least 28 days after the drug withdrawal. Clozapine, but not haloperidol, reduced METH-induced cognitive impairment. Hyperphosphorylation of ERK1/2 was found in the prefrontal cortex of mice exposed to the novel objects, but was abolished in mice treated with METH. Inhibition of ERK1/2 by the microinjection of PD98059 into the prefrontal cortex resulted in cognitive impairment. Conclusions: These results suggest that repeated METH treatment induces cognitive impairment, which is associated with the dysfunction of the ERK1/2 pathway in the prefrontal cortex.

Original languageEnglish
Pages (from-to)75-84
Number of pages10
JournalBiological Psychiatry
Volume59
Issue number1
DOIs
Publication statusPublished - 01-01-2006

All Science Journal Classification (ASJC) codes

  • Biological Psychiatry

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