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Neuropharmacology. 2013 Dec;75:399-406. doi: 10.1016/j.neuropharm.2013.08.017. Epub 2013 Aug 28.

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

Author information

  • 1Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska Science Park, Medicinaregatan 8A, 413 46 Gothenburg, Sweden. Electronic address: marie.nilsson@psychiat.gu.se.
  • 2Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska Science Park, Medicinaregatan 8A, 413 46 Gothenburg, Sweden.

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.

Copyright © 2013 Elsevier Ltd. All rights reserved.

KEYWORDS:

Cognition; ISI; NMRI mice; Object location; Scopolamine; Spatial recognition memory; inter-session interval

PMID:
23994443
[PubMed - indexed for MEDLINE]
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