The monoaminergic stabilizer (−)-OSU6162 reverses delay-dependent natural forgetting and improves memory impairment induced by scopolamine in mice

Abstract

The aim of the present study was to evaluate the effect of the monoaminergic stabilizer (−)-OSU6162 on spatial recognition memory. Male NMRI mice were tested in the object location model which is based on the animals' inherent interest to examine changes in their environment: The animals' propensity to explore relocated objects in relation to unaltered objects, presented in two different sessions (sample and trial), was studied. In a first series of experiments the effect of (−)-OSU6162 on natural forgetting was evaluated. With an inter-session interval (ISI) of 30 min or an hour, untreated mice spent longer time exploring the displaced object, but when the time between sessions was as long as 6 h, the mice did not identify the displaced object. However, using the 6 h ISI design we found that (−)-OSU6162 in doses up to 30 μmol/kg, given directly after the sample session, caused an increased interest for the displaced object. Twenty-four hours after administration, (−)-OSU6162 was still effective in facilitating identification of the displaced object. We also evaluated the effect of (−)-OSU6162 on scopolamine-induced memory deficits in this model – the two agents were given 30 min before the sample session and the ISI was one hour. Under these conditions scopolamine induced a deficit in object location memory and this effect was counteracted by (−)-OSU6162. The data from the present study suggest that (−)-OSU6162 prolongs object location memory in normal mice and reverses scopolamine-induced memory deficits. (−)-OSU6162 might be a valuable drug candidate for memory deficits and other cognitive impairments.