ERK5 inhibitor BIX02189 attenuates methamphetamine-induced hyperactivity by modulating microglial activation in the striatum

Osamu Nakagawasai; Kohei Takahashi; Yuki Miura; Wataru Nemoto; Yutaro Obara; Koichi Tan-No

Journal of Pharmacological Sciences (Mar 2022)

ERK5 inhibitor BIX02189 attenuates methamphetamine-induced hyperactivity by modulating microglial activation in the striatum

Osamu Nakagawasai,
Kohei Takahashi,
Yuki Miura,
Wataru Nemoto,
Yutaro Obara,
Koichi Tan-No

Affiliations

Osamu Nakagawasai: Division of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi, 981-8558, Japan; Corresponding author. Fax: +81 22 727 0123.
Kohei Takahashi: Division of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi, 981-8558, Japan; Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan
Yuki Miura: Division of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi, 981-8558, Japan
Wataru Nemoto: Division of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi, 981-8558, Japan
Yutaro Obara: Department of Pharmacology, Yamagata University School of Medicine, Iida-Nishi 2-2-2, Yamagata, 990-9585, Japan
Koichi Tan-No: Division of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi, 981-8558, Japan

Journal volume & issue: Vol. 148, no. 3
pp. 326 – 330

Abstract

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Extracellular signal-regulated protein kinase 5 (ERK5) has various physiological functions. However, the physiological role of ERK5 in the treatment of mice with an illicit drug such as methamphetamine (METH) remains unknown. We revealed that mice treated with METH showed hyperactivity, and increased p-ERK5 and Iba1 (a microglia marker) levels in the striatum. Additionally, these changes were inhibited by pretreatment with the ERK5 inhibitor BIX02189. The results suggest that METH-induced hyperactivity is associated with the activation of microglia via p-ERK5 in the striatum. Thus, the ERK5 pathway components in the central nervous system are potential therapeutic targets for preventing METH addiction.

Published in Journal of Pharmacological Sciences

ISSN: 1347-8613 (Print)
Publisher: Elsevier
Country of publisher: Japan
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.journals.elsevier.com/journal-of-pharmacological-sciences

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