Involvement of agmatine in antidepressant-like effect of HMG-CoA reductase inhibitors in mice.

摘要: Abstract 3-Hydroxy-3-methyl-glutaryl-co-enzyme–A (HMG-CoA) reductase inhibitors (statins) are popularly used for the treatment of obesity and hypercholesterolemia with established safety profile. Statins exhibits a wide range neurobehavioral effects in addition to their peripheral actions, may be beneficial psychiatric conditions. Present study investigated role agmatine imidazoline receptors antidepressant-like effect statins mouse forced swimming test (FST). The atorvastatin (5 mg/kg, p.o.) simvastatin (10 mg/kg, was potentiated by pretreatment i.p.) as well drugs known increase endogenous levels brain viz., L-arginine (40 μg/mouse, i.c.v.), an biosynthetic precursor; arcaine (50 i.c.v), agmatinase inhibitor; aminoguanidine (6.5 diamine oxidase inhibitor. Further, both increased within hippocampus prefrontal cortex. Conversely, prior administration I1 receptor antagonist, efaroxan (1 mg/kg, I2 idazoxan (0.25 mg/kg, blocked synergistic combination agmatine. These results demonstrate involvement suggest potential therapeutic target depressive disorders.