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Strain-dependent effects of cognitive enhancers in the mouse

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Summary.

A series of cognitive enhancers (CEs) have been reported to increase spatial memory in rodents, information on behavioral effects, however, is limited. The aim of the study was therefore to examine the behavioral effects of three CEs in two well-documented inbred mouse strains.

C57BL/6J and DBA/2 mice were administered intraperitonial. D-cycloserine (DCS; NMDA receptor agonist), 1-(4-Amino-5-chloro-2-methoxyphenyl)-3-[1-butyl-4-piperidinyl]-1-propanone hydrochloride (RS67333; 5HT4-receptor agonist), and (R)-4-{[2-(1-methyl-2-pyrrolidinyl)ethyl]thio}phenol hydrochloride (SIB-1553A; β-4-nicotinic receptor agonist) and tested in the open field (OF), elevated plus maze (EPM), neurological observational battery and rota-rod. Cognitive performance was tested in the Morris water maze.

All compounds modified behavioral performance in the OF, DCS showed an anxiolytic effect in the EPM, and differences in the observational battery were observed i.e. vestibular drop was decreased by SIB-1553A and RS67333 treatment in C57BL/6J and increased with DCS treatment in DBA/2 mice. In the rota rod SIB-1553A improved motor performance.

DCS effects on learning and memory was comparable to controls whereas the other compounds impaired performance in the Morris water maze.

In conclusion, behavioral testing of CEs in the mouse revealed significant changes that may have to be taken into account for evaluation of CEs, interpretation of cognitive studies and warrant further neurotoxicological studies. Moreover, strain-dependent differences were observed that in turn may confound results obtained from behavioral and cognitive testing.

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Abbreviations

CEs:

cognitive enhancers

DCS:

D-cycloserine

EPM:

Elevated plus maze

5-HT:

5-Hydroxytryptamine

MWM:

morris water maze

NMDA:

N-methyl-D-aspartate

OF:

open field

RS67333:

1-(4-Amino-5-chloro-2-methoxyphenyl)-3-[1-butyl-4-piperidinyl]-1-propanone hydrochloride

SIB-1553A:

(R)-4-{[2-(1-methyl-2-pyrrolidinyl)ethyl]thio} phenol hydrochloride

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Authors and Affiliations

  1. Department of Pediatrics, Division of Pediatric Neuroscience, Medical University of Vienna, Vienna, Austria

    B. Sunyer, S. Patil, C. Frischer & G. Lubec

  2. Core Unit of Biomedical Research, Division of Laboratory Animal Science and Genetics, Medical University of Vienna, Vienna, Austria

    H. Hoeger

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  1. B. Sunyer
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  2. S. Patil
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  3. C. Frischer
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  4. H. Hoeger
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  5. G. Lubec
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Authors’ address: o. Univ. Prof. Dr. Gert Lubec, Department of Pediatrics, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria

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Sunyer, B., Patil, S., Frischer, C. et al. Strain-dependent effects of cognitive enhancers in the mouse. Amino Acids 34, 485–495 (2008). https://doi.org/10.1007/s00726-007-0511-6

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