title: Dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory memory tasks in mice.
abstract: Pre-clinical and clinical studies on dimebon (dimebolin or latrepirdine) have demonstrated its use as a cognitive enhancer. Here, we show that dimebon administered to 3-month-old C57BL6N mice 15 min prior to training in both appetitive and inhibitory learning tasks via repeated (0.1 mg/kg) and acute (0.5 mg/kg) i.p. injections, respectively, increases memory scores. Acute treatment with dimebon was found to enhance inhibitory learning, as also shown in the step-down avoidance paradigm in 7-month-old mice. Bolus administration of dimebon did not affect the animals' locomotion, exploration or anxiety-like behaviour, with the exception of exploratory behaviour in older mice in the novel cage test. In a model of appetitive learning, a spatial version of the Y-maze, dimebon increased the rate of correct choices and decreased the latency of accessing a water reward after water deprivation, and increased the duration of drinking behaviour during training/testing procedures. Repeated treatment with dimebon did not alter the behaviours in other tests or water consumption. Acute treatment of water-deprived and non-water-deprived mice with dimebon also did not affect their water intake. Our data suggest that dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory tasks in mice.
authors.affiliation: School for Mental Health and Neuroscience, Department of Neuroscience, Maastricht University, Universiteitssingel 50, NL 6229 ER Maastricht, The Netherlands.
authors.forename: Julie
authors.initials: J
authors.lastname: Vignisse
authors.forename: Harry W M
authors.initials: HW
authors.lastname: Steinbusch
authors.forename: Alexei
authors.initials: A
authors.lastname: Bolkunov
authors.forename: Joao
authors.initials: J
authors.lastname: Nunes
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Santos
authors.forename: Christian
authors.initials: C
authors.lastname: Grandfils
authors.forename: Sergei
authors.initials: S
authors.lastname: Bachurin
authors.forename: Tatyana
authors.initials: T
authors.lastname: Strekalova
mesh_terms: D000818:Animals; D001007:Anxiety; D001070:Appetitive Behavior / Q000187:drug effects*; D001362:Avoidance Learning / Q000187:drug effects; D004326:Drinking / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology*; D007858:Learning / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018697:Nootropic Agents / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D007211:Indoles; D018697:Nootropic Agents; C010119:latrepirdine