Agmatine protects against scopolamine-induced water maze performance impairment and hippocampal ERK and Akt inactivation

Cholinergic brain activity plays a significant role in memory. Scopolamine a muscarinic cholinergic antagonist is known to induce impairment in Morris water maze performance, the task which is mainly dependent on the hippocampus. It is suggested that hippocampal ERK and Akt activation play roles in synaptic plasticity and some types of learning and memory. Agmatine, a polyamine derived from l-arginine decarboxylation, is recently shown to exert some neuroprotective effects. This study was aimed to investigate if agmatine could reverse scopolamine-induced memory impairment and possible hippocampal ERK and Akt activity alteration. Adult male Sprague-Dawley rats weighing 200–250 g were randomly assigned into 5 groups. The animals were trained for 3 days in Morris water maze and in day 4 their memory retention was assessed in probe trial which was consisted of a 60 s trial with no platform. Scopolamine (1 mg/kg/ip) or saline were injected 30 min and agmatine (20 or 40 mg/kg/ip) was administered 60 min before each session. The hippocampi were isolated after behavioral studies and western blotting studies on hippocampal lysates were done to determine the levels of activated ERK and Akt. Scopolamine treatment not only impaired water maze learning and memory, but also decreased the amount of phosphorylated (activated) ERK and Akt. Agmatine pre-treatment prevented both the learning impairment and hippocampal ERK and Akt inactivation induced by scopolamine. It seems that agmatine may act as a candidate substance against amnesia.

► Scopolamine treatment not only deteriorates Morris water maze learning and memory but also suppressed hippocampal ERK and Akt activation.
► Agmatine prevented scopolamine-induced memory impairment.
► Agmatine prevented the reduction of hippocampal ERK and Akt activation.