Agmatine attenuates depressive-like behavior and hippocampal oxidative stress following amyloid β (Aβ1-40) administration in mice

•Agmatine attenuates depressive-like behavior induced by Aβ in mice.•Agmatine attenuates Aβ-induced increase in hippocampal lipid peroxidation levels.•Agmatine protected against the Aβ-induced decrease in hippocampal catalase activity. Depression is one of the most common psychiatric symptoms in Alzheimer's disease (AD), and several studies have shown that oxidative stress plays a key role in the etiopathology of both AD and depression. Clinical studies indicate reduced efficacy of the current antidepressants for the treatment of depression in AD. In this regard, agmatine emerges as a neuroprotective agent that presents diverse effects, including antidepressant and antioxidant properties. Here we investigated the antioxidant and antidepressant-like effects of agmatine in a mouse model of AD induced by a single intracerebroventricular (i.c.v.) administration of amyloid-β 1–40 (Aβ). Mice were treated with agmatine (10 mg/kg, intraperitoneally) once a day during seven consecutive days. The first administration of agmatine was 24 h before the i.c.v. injection of aggregated Aβ 1–40 (400 pmol/mouse). Ten days after Aβ injection, mice were evaluated in the forced swimming test (FST) and open field test for assessment of depressive-like behavior and locomotor activity, respectively. Oxidative parameters were evaluated in the hippocampus of mice 24 h after Aβ injection. Agmatine prevented Aβ-induced increase in hippocampal lipid peroxidation levels and Aβ-induced decrease in catalase activity. In addition, agmatine prevented the increase in immobility time in the FST and the decrease in the latency to the first immobility episode induced by Aβ, without changing locomotion in the open field test. These results demonstrate the antioxidant and antidepressant-like effects of agmatine in a mouse model of AD, indicating the potential of agmatine for the treatment of depression associated to AD.