Systemic administration of ZLc-002 exerts anxiolytic-like effects by dissociation of nNOS from CAPON in adult mice
Autor: | Na Li, Lei Chang, Hu-Jiang Shi, Li-Juan Zhu |
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Rok vydání: | 2020 |
Předmět: |
Male
0301 basic medicine Elevated plus maze Biophysics Nitric Oxide Synthase Type I Hippocampal formation Pharmacology Capon Hippocampus Biochemistry Anxiolytic like Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Dosing Enzyme Inhibitors Maze Learning Molecular Biology Microinjection Adaptor Proteins Signal Transducing Mice Inbred ICR Behavior Animal Dose-Response Relationship Drug business.industry Cell Biology Anxiety Disorders Disease Models Animal 030104 developmental biology Anti-Anxiety Agents 030220 oncology & carcinogenesis Systemic administration Anxiety medicine.symptom business Injections Intraperitoneal |
Zdroj: | Biochemical and Biophysical Research Communications. 523:299-306 |
ISSN: | 0006-291X |
Popis: | Anxiety is recognized as primary clinical phenotype of psychiatric disorders. However, many patients with anxiety have not yet received effective treatment. Our previous study demonstrated that hippocampal nNOS-CAPON interaction is implicated in anxiety-related behaviors, and blocking nNOS-CAPON interaction in the hippocampus produces anxiolytic-like effects. Here, ZLc-002, a small molecule inhibitor of nNOS-CAPON coupling, was evaluated for anxiolytic-like properties after systemic administered using anxiety behavioral tests, including open-field (OF), elevated plus maze (EPM), novelty-suppressed feeding (NSF) and light-dark (LD) tests. We reported that ZLc-002 when administered intraperitoneally at the dose of 40 or 80 mg/kg/d for 14 days produces anxiolytic-like effects. Furthermore, the similar effects of ZLc-002 were observed when administered intravenously at the dose of 10, 20 or 40 mg/kg/d for 7 days. More importantly, the mice dosing with 80 mg/kg/d ZLc-002 intraperitoneally or 40 mg/kg/d ZLc-002 intravenously for 3 days exerted significant behavioral effects. However, intragastric administration with ZLc-002 was devoid of effect on anxiety behaviors, even at high doses. Furthermore, intraperitoneal or intravenous treatment of ZLc-002 significantly disrupted the interaction between nNOS and CAPON in the hippocampus of adult mice, and there was a significant anxiolytic-like effect of ZLc-002 at day 3 after intrahippocampal microinjection. Our results verified that systemic administration of putative small molecule inhibitor of nNOS-CAPON can be used for the treatment of anxiety disorders. |
Databáze: | OpenAIRE |
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