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

• Published in: Journal of pharmacological sciences Vol. 148; no. 3; pp. 326 - 330
• Main Authors: Nakagawasai, Osamu, Takahashi, Kohei, Miura, Yuki, Nemoto, Wataru, Obara, Yutaro, Tan-No, Koichi
• Format: Journal Article
• Language: English
• Published: Japan Elsevier B.V 01.03.2022; Elsevier
• Subjects: Aniline Compounds - pharmacology; Aniline Compounds - therapeutic use; Animals; BIX02189; Calcium-Binding Proteins - metabolism; Corpus Striatum - cytology; Corpus Striatum - metabolism; ERK5; 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; Striatum; Substance-Related Disorders - prevention & control; Striatum; BIX02189; ERK5
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1016/j.jphs.2022.01.009

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.