Comparative effects of the α7 nicotinic partial agonist, S 24795, and the cholinesterase inhibitor, donepezil, against aging-related deficits in declarative and working memory in mice

A. Marighetto, S. Valerio, A. Desmedt, J. N. Philippin, C. Trocmé-Thibierge, P. Morain
Psychopharmacology. 2008-02-12; 197(3): 499-508
DOI: 10.1007/s00213-007-1063-x

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1. Psychopharmacology (Berl). 2008 Apr;197(3):499-508. doi:
10.1007/s00213-007-1063-x. Epub 2008 Feb 12.

Comparative effects of the alpha7 nicotinic partial agonist, S 24795, and the
cholinesterase inhibitor, donepezil, against aging-related deficits in
declarative and working memory in mice.

Marighetto A(1), Valerio S, Desmedt A, Philippin JN, Trocmé-Thibierge C, Morain
P.

Author information:
(1)Centre Neurosciences Intégratives et Cognitives, Université Bordeaux 1, CNRS
5228, Talence, France.

INTRODUCTION: The comparative effects of a newly described specific alpha7 nAChR
partial agonist, S 24795, and a cholinesterase inhibitor, donepezil, currently
used as a symptomatic Alzheimer’s disease treatment were studied in two mouse
models of aging-related memory deficits.
MATERIALS AND METHODS: We employed radial arm-maze paradigms assessing short-term
working memory (STWM, experiment A) and mnemonic flexibility, a cardinal property
of long-term declarative (LTDM, experiment B). Both compounds were administered
daily at 0.3 and 1 mg/kg subcutaneously (~3 weeks).
RESULTS: In the STWM experiment, vehicle-treated aged mice displayed a severe and
persistent deficit in the retention of successive arm visits in comparison to
younger controls. S 24795 at 1 mg/kg (trends at 0.3 mg/kg) and donepezil at 0.3
mg/kg (but not 1 mg/kg) exerted beneficial effects on this deficit: The
performance of aged mice treated with these drugs remarkably increased across the
testing days and almost reached young adult performance level. In the critical
test trials of memory flexibility (i.e., LTDM), in experiment B, S 24795 at 1
mg/kg (trends at 0.3 mg/kg) and donepezil at the dose of 1 mg/kg (but not 0.3
mg/kg) improved aged mice performance.
CONCLUSION: This preclinical demonstration that S 24795 restored specific
age-related memory deficits with as much efficacy as donepezil adds to recent
literature in highlighting the potential interest of an alpha7 nAChR drug as a
symptomatic AD therapeutic.

DOI: 10.1007/s00213-007-1063-x
PMID: 18265960 [Indexed for MEDLINE]


Auteurs Bordeaux Neurocampus