Abstract
In the present article, we describe a new protocol for the inhibitory avoidance test, with a dual purpose: (1) to provide a leß variable and more reliable aßeßment of the efficacy of potential cognitive enhancers in antagonizing scopolamine-induced long-term-memory deficits, and (2) to secure a high throughput for pharmacological screening of cognitive enhancers. The new protocol consists of two acquisition trials that are followed 24 h later by a single retention trial. In the present study, this protocol clearly dißociated the frequency distributions of retention latencies between scopolamine- and vehicle-treated groups and allowed validation by means of two acetylcholinesterase inhibitors—tacrine and donepezil—that proved to be active in counteracting the scopolamine-induced memory deficit. This protocol also produced stability of the behavioral response to pharmacological agents over a 3-year period. A statistical power analysis indicated that, depending on the efficacy of the drug/dose, a sample size of 5–12 mice was required in order to show a reversal of the scopolamineinduced memory deficit. The double-trial acquisition protocol is suitable for testing cognitive enhancers, while also providing a clearly enhanced throughput.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Balogh, S. A., & Wehner, J. M. (2003). Inbred mouse strain differences in the establishment of long-term fear memory. Behavioural Brain Research, 140, 97–106.
Banfi, S., Cornelli, U., Fonio, W., & Dorigotti, L. (1982). A screening method for substances potentially active on learning and memory. Journal of Pharmacological Methods, 8, 255–263.
Bartus, R. T., Dean, R. L., Goas, J. A., & Lippa, A. S. (1980). Age-related changes in paßive avoidance retention: Modulation with dietary choline. Science, 209, 301–303.
Bohdanecký, Z., & Jarvik, M. E. (1967). Impairment of one-trial paßive avoidance learning in mice by scopolamine, scopolamine methylbromide, and physostigmine. International Journal of Neuropharmacology, 6, 217–222.
Brunner, D., Nestler, E., & Leahy, E. (2002). In need of high-throughput behavioral systems. Drug Discovery Today, 7(18 Suppl.), S107-S112.
Castellano, C., & Puglisi-Allegra, S. (1983). Strain-dependent modulation of memory by streß in mice. Behavioral & Neural Biology, 38, 133–138.
Caulfield, M. P. (1993). Muscarinic receptors—Characterization, coupling and function. Pharmacology & Therapeutics, 58, 319–379.
Crawley, J. N., Belknap, J. K., Collins, A., Crabbe, J. C., Frankel, W., Henderson, N., et al. (1997). Behavioral phenotypes of inbred mouse strains: Implications and recommendations for molecular studies. Psychopharmacology, 132, 107–124.
Dawson, G. R., & Iversen, S. D. (1993). The effects of novel cholinesterase inhibitors and selective muscarinic receptor agonists in tests of reference and working memory. Behavioural Brain Research, 57, 143–153.
Dilts, S. L., & Berry, C. A. (1967). Effect of cholinergic drugs on paßive avoidance in the mouse. Journal of Pharmacology & Experimental Therapeutics, 158, 279–285.
Ebert, U., & Kirch, W. (1998). Scopolamine model of dementia: Electroencephalogram findings and cognitive performance. European Journal of Clinical Investigation, 28, 944–949.
Elrod, K., & Buccafusco, J. J. (1988). An evaluation of the mechanism of scopolamine-induced impairment in two paßive avoidance protocols. Pharmacology, Biochemistry, & Behavior, 29, 15–21.
Graham, J. H., & Buccafusco, J. J. (2001). Inhibitory avoidance behavior and memory aßeßment. In J. J. Buccafusco (Ed.), Methods of behavior analysis in neuroscience (pp. 141–151). London: CCR.
Jarvik, M. E., & Kopp, R. (1967). An improved one-trial paßive avoidance learning situation. Psychological Reports, 21, 221–224.
Kallman, M. J., & Condie, L. W., Jr. (1985). A test battery for screening behavioral teratogens in mice. Neurobehavioral Toxicology & Teratology, 7, 727–731.
Koide, T., Moriwaki, K., Ikeda, K., Niki, H., & Shiroishi, T. (2000). Multi-phenotype behavioral characterization of inbred strains derived from wild stocks of Mus musculus. Mammalian Genome, 8, 664–670.
Lamberty, Y., & Gower, A. J. (1990). Age-related changes in spontaneous behavior and learning in NMRI mice from maturity to middle age. Physiology & Behavior, 47, 1137–1144.
Pan, S. Y., Han, Y. F., Yu, Z. L., Yang, R., Dong, H., & Ko, K. M. (2006). Evaluation of acute tacrine treatment on paßive-avoidance response, open-field behavior, and toxicity in 17- and 30-day-old mice. Pharmacology, Biochemistry, & Behavior, 85, 50–56.
Ray, D., & Nagy, Z. M. (1978). Emerging cholinergic mechanisms and ontogeny of response inhibition in the mouse. Journal of Comparative & Physiological Psychology, 92, 335–349.
Rush, D. (1988). Scopolamine amnesia of paßive avoidance: A deficit of information acquisition. Behavioral & Neural Biology, 50, 255–274.
Sahgal, A. (1993). Paßive avoidance procedures. In A. Shagal (Ed.), Behavioural neuroscience: A practical approach (Vol. 1, pp. 49–56). New York: Oxford University Preß.
Sarter, M., Hagan, J., & Dudchenko, P. (1992). Behavioral screening for cognition enhancers: From indiscriminate to valid testing. Part II. Psychopharmacology, 107, 461–473.
Saxena, G., Singh, S. P., Agrawal, R., & Nath, C. (2008). Effect of donepezil and tacrine on oxidative streß in intracerebral streptozotocin-induced model of dementia in mice. European Journal of Pharmacology, 581, 283–289.
Shutske, G. M., Pierrat, F. A., Kapples, K. J., Cornfeldt, M. L., Szewczak, M. R., Huger, F. P., et al. (1989). 9-Amino-1,2,3,4-tetrahydroacridin-1-ols: Synthesis and evaluation as potential Alzheimer’s disease therapeutics. Journal of Medicinal Chemistry, 32, 1805–1813.
Wehner, J. M., & Balogh, S. A. (2003). Phenotyping mice for learning and memory: Traditional tasks, modifications of traditional tasks, and application of new tasks [Society for Neuroscience, Short course].
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Detrait, E.R.A.Y., Hanon, É., Dardenne, B. et al. The inhibitory avoidance test optimized for discovery of cognitive enhancers. Behavior Research Methods 41, 805–811 (2009). https://doi.org/10.3758/BRM.41.3.805
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.3758/BRM.41.3.805