Rho kinase inhibitors ameliorate cognitive impairment in a male mouse model of methamphetamine-induced schizophrenia

• DOI: 10.1016/j.phrs.2023.106838
• Publication Date: 2023-06-28T17:50:53Z
• Authors: Jingzhu Liao; Geyao Dong; Wenjun Zhu; Bolati Wulaer; Hiroyuki Mizoguchi; Masahito Sawahata; Yue Liu; Kozo Kaibuchi; Norio Ozaki; Toshitaka Nabeshima; Taku Nagai; Kiyofumi Yamada
• Keywords: Fasudil; Infralimbic cortex; Methamphetamine; Meth-

Schizophrenia (SCZ) is a severe psychiatric disorder characterized by positive symptoms, negative and cognitive deficits. Current antipsychotic treatment in SCZ improves symptoms but has major side effects little impact on impairment. The pathoetiology of remains unclear, known to involve small GTPase signaling. Rho kinase, an effector Rho, highly expressed the brain plays role neurite elongation neuronal architecture. This study used touchscreen-based visual discrimination (VD) task investigate kinase inhibitors impairment methamphetamine (METH)-treated male mouse model SCZ. Systemic injection inhibitor fasudil dose-dependently ameliorated METH-induced VD Fasudil also significantly suppressed increase number c-Fos-positive cells infralimbic medial prefrontal cortex (infralimbic mPFC) dorsomedial striatum (DMS) following METH treatment. Bilateral microinjections Y-27632, another inhibitor, into mPFC or DMS Two proteins downstream myosin phosphatase-targeting subunit 1 (MYPT1; Thr696) light chain 2 (MLC2; Thr18/Ser19), exhibited increased phosphorylation DMS, respectively, after treatment, inhibited these increases. Oral administration haloperidol impairment, while clozapine had effect. hyperactivity, no These results suggest that activates which leads mice. ameliorate perhaps via cortico-striatal circuit.