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

doi:10.1016/j.jphs.2022.01.009

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

J Pharmacol Sci. 2022 Mar;148(3):326-330. doi: 10.1016/j.jphs.2022.01.009. Epub 2022 Jan 23.

Authors

Osamu Nakagawasai¹, Kohei Takahashi², Yuki Miura³, Wataru Nemoto³, Yutaro Obara⁴, Koichi Tan-No³

Affiliations

¹ Division of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi, 981-8558, Japan. Electronic address: osamun@tohoku-mpu.ac.jp.
² 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.
³ Division of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi, 981-8558, Japan.
⁴ Department of Pharmacology, Yamagata University School of Medicine, Iida-Nishi 2-2-2, Yamagata, 990-9585, Japan.

PMID: 35177212
DOI: 10.1016/j.jphs.2022.01.009

Abstract

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.

Keywords: BIX02189; ERK5; Striatum.

MeSH terms

Aniline Compounds / pharmacology*
Aniline Compounds / therapeutic use
Animals
Calcium-Binding Proteins / metabolism
Corpus Striatum / cytology*
Corpus Striatum / metabolism
Hyperkinesis / chemically induced*
Hyperkinesis / drug therapy*
Indoles / pharmacology*
Indoles / therapeutic use
Methantheline / adverse effects*
Mice
Microfilament Proteins / metabolism
Microglia / drug effects*
Microglia / metabolism
Mitogen-Activated Protein Kinase 7 / antagonists & inhibitors*
Mitogen-Activated Protein Kinase 7 / metabolism
Mitogen-Activated Protein Kinase 7 / physiology*
Psychomotor Agitation
Substance-Related Disorders / prevention & control

Substances

Aif1 protein, mouse
Aniline Compounds
BIX 02189
Calcium-Binding Proteins
Indoles
Microfilament Proteins
Methantheline
Mitogen-Activated Protein Kinase 7