title: 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.
authors.affiliation: Institute 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.
authors.forename: Marie K L
authors.initials: MK
authors.lastname: Nilsson
authors.affiliation: Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska Science Park, Medicinaregatan 8A, 413 46 Gothenburg, Sweden.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Carlsson
mesh_terms: D000818:Animals; D004192:Discrimination, Psychological / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use*; D012601:Scopolamine; D013997:Time Factors
chemical_list: D018696:Neuroprotective Agents; D010880:Piperidines; C109513:OSU 6162; D012601:Scopolamine
keywords: Cognition; ISI; NMRI mice; Object location; Scopolamine; Spatial recognition memory; inter-session interval