A Servier paper from SFN comparing S-18986 with an ACHase inhibitor. There may be a typo in this abstract though, since they have the lower dose as effective while the higher dose wasn't. Too much wine perhaps -
>>> Program#/Poster#: 273.20/LL30
Title: S 18986 and donepezil totally reversed the age-induced contextual memory deficits in C57BL/6 mice
Location: Georgia World Congress Center: Halls B3-B5
Presentation Start/End Time: Sunday, Oct 15, 2006, 4:00 PM - 5:00 PM
Authors: D. BERACOCHEA1, J. PHILIPPIN1, K. BERNARD2, *P. MORAIN2;
1Université de Bordeaux-UFR biologie, CNRS UMR-5106 - Lab. de Neurosciences Cognitives, 33405 Talence, FRANCE, 2Neuropsychiatrie, Institut de Recherches Internationales Servier, 92415 Courbevoie Ced, FRANCE.
Our study purported to probe the effects of S 18986, a new positive allosteric modulator of AMPA-type receptors in a mouse model of contextual memory deficits induced by ageing. S 18986 was compared to donepezil, an cholinesterase inhibitor with beneficial memory effects in minor forms of Alzheimer’s disease.
Mice (14-15 month-old) underwent a behavioral task designed to study simultaneously the retrieval of stable (spatial) and flexible (contextual and serial) information (Celerier et al, 2004). The task involved the learning of two consecutive spatial discriminations in a four hole-board apparatus; these were performed on two different floors (white versus black) and the rewarded holes (one baited hole per discrimination) were diagonally opposite. Memory testing, performed on independent groups, occurred 24 hrs after the acquisition phase. During the test, mice were placed either on the floor of the 1rst or of the 2nd discrimination.
Mice underwent a chronic (9 days) per os administration of either donepezil (at 0.3 mg/kg) or S 18986 (at 0.1-0.3 and 1.0 mg/kg). They were compared to placebo-treated mice under similar conditions and to young (5 month old) mice. The two last administrations were given one hour before the acquisition (day 8) and test (day 9) phases. Placebo-treated mice exhibited a severe memory deficit in the remembering of the first discrimination as opposed to 5 month-old mice. The deficit in aged mice was evidenced by a significant fall of head-dips into the previously baited hole, and by an increase of interference. Both donepezil at 0.3 mg/kg and S 18986 at 0.1 mg/kg significantly reversed the memory impairments observed in 14 month-old mice; the other S 18986 doses had no effect. The memory-enhancing effects of both donepezil and S 18986 resulted from a lower rate of interference. Thus, S 18986 emerges as having effective beneficial impact on contextual memory processes among aged mice. <<<
