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The value of spontaneous alternation behavior (SAB) as a test of retention in pharmacological investigations of memory
Abstract
Because of its reliance on memory, the tendency for rats, mice and other animals to alternate successive choices of T- or Y-maze arms has assumed considerable popularity in pharmacological studies of spatial memory as a quick and simple measure of retention that avoids the need for extensive training and the use of conventional reinforcers. Two forms of this tendency have been utilized, namely two-trial and continuous spontaneous alternation behavior (SAB). However, as the behavior can also reflect drug-related changes in sensory/attentional, motivational and performance processes, SAB should not be unquestionably accepted as a measure of memory alone. While assessments of post-acquisition drug effects on longer term memory may be possible through the appropriate timing of drug administration, this is more problematic if SAB is used as a measure of shorter term memory. Even though SAB can be a useful index of responsiveness to novelty, its value as a measure of retention is less certain. In this latter respect, a possible alternative to SAB testing might be the recently developed form of the related procedure, responsiveness to change.
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“A symmetrical Y maze was used to evaluate spatial working memory [49].”
From Selective suppression of the α isoform of p38 MAPK rescues late-stage tau pathology (2016) · cites this paper as [49]
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“If a mouse remained immobile or failed to explore all three arms, it was excluded from the study61.”
From MT1-MMP inhibition rejuvenates ageing brain and rescues cognitive deficits in obesity (2025) · cites this paper as [61]
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“𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑐𝑜𝑚𝑝𝑙𝑒𝑡𝑒 𝑡𝑟𝑖𝑎𝑑 𝑒𝑛𝑡𝑒𝑟𝑖𝑒𝑠 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑎𝑟𝑚 𝑒𝑛𝑡𝑒𝑟𝑖𝑒𝑠 − 2 𝑥 100 (Hughes, 2004; Oriel and Kofman, 2015).”
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“Our Y-maze results, confirmed with the everyday like working memory task in the radial maze, show that our mice have a deficit of working memory in the absence of Vangl2 (Hughes, 2004).”
Afridi, M. B., Shah, S. W. A., Hussain, H., Elhenawy, A. A., Mujtaba, M., Al-Otaibi, J. S., & Khan, H. Z. (2025) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2025.178193 · Cited by 3
Fernandez, R. F., Fallatah, W., Ji, Y., Jones, J. W., Johnson, C. C., Tressler, C. M., Glunde, K., Ali, R., Moser, A. B., Wolfgang, M. J., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-67542-6 · Cited by 3
“69,70.”
A New Approach for Exploring Reperfusion Brain Damage in Hypoxic Ischemic Encephalopathy
Zhang, T., Zhang, Z., Geng, J., Lin, K., Lin, X., Jiao, M., Zhu, J., Guo, X., & Lin, Z. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03645-9 · Cited by 3
“The video is recorded and the data is analyzed according to Robert’s methodological description [15].”
Song, H., Xie, Y., Fang, Y., Lin, J., Wang, L., Gan, C., Aschner, M., & Jiang, Y. (2024) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.14033 · Cited by 3
“…This gives the animal the ability to remember which arm has been visited a fewer number of times recently, and therefore, this test is used to assess working memory, which is a form of short-term memory 23,24 During the training phase, the rats were allowed to freely explore two arms for 5 min.”
MethodFazekas, C. L., Török, B., Correia, P., Chaves, T., Bellardie, M., Sipos, E., Horváth, H. R., Gaszner, B., Dóra, F., Dobolyi, Á., et al. (2024) · eNeuro · doi:10.1523/eneuro.0332-23.2024 · Cited by 3
“This test detects the short-term learning and memory of rodents, re fl ected by continuous spontaneous alternation (Hughes, 2004).”
BackgroundBrouzi, M. Y. E., Lamtai, M., Fath, N., Rezqaoui, A., Zghari, O., Hamzaoui, A. E., Ibouzine‐Dine, L., Hessni, A. E., & Mesfioui, A. (2024) · BioMetals · doi:10.1007/s10534-024-00618-w · Cited by 3
“The Y maze test assesses the spontaneous alternation capacity of working memory in rodents, without the use of a reinforcer such as food (Hughes 2004).”
Park, W., Kim, Y., & Cho, S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25158526 · Cited by 3
“The Y-maze test was performed to assess short-term working memory (Y-arm length, 40 cm; bottom arm width, 4 cm; wall height, 12 cm) [57].”
MethodGharib, O. A., & Karam, H. M. (2024) · Pharmaceutical Chemistry Journal · doi:10.1007/s11094-025-03285-4 · Cited by 3
Gupta, S., Rishi, V., & Aggarwal, A. (2025) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2025.110050 · Cited by 3
Maki, A. E., Morris, K. A., Catherman, K., Chen, X., Hatcher, N. G., Gold, P. E., & Sweedler, J. V. (2014) · Pharmacology Research & Perspectives · doi:10.1002/prp2.37 · Cited by 3
“often in pharmacological studies of memory including in combination with microdialysis methods (Ragozzino et al. 1996; McNay et al. 2000, 2001; Hughes 2004; Chang and Gold 2008; De Bundel et al. 2009).”
Crowley, E. K., Grabrucker, S., Long-Smith, C. M., Stack, A., O’Gorman, D. M., & Nolan, Y. M. (2021) · Journal of Medicinal Food · doi:10.1089/jmf.2020.0213 · Cited by 3
“4,22 Although spontaneous alternations 23 and novel object recognition 17 are both hippocampal-dependent behaviors, pattern separation has been shown to be dependent on AHN.”
Nigella sativa oil alleviates doxorubicin-induced cardiomyopathy and neurobehavioral changes in mice
Anwar, M. J., Alenezi, S. K., Azam, F., Mahmood, D., Imam, F., & Alharbi, K. S. (2022) · Asian Pacific Journal of Tropical Biomedicine · doi:10.4103/2221-1691.350179 · Cited by 3
Real-time changes in hippocampal energy demands during a spatial working memory task
Kealy, J., Bennett, R., Woods, B., & Lowry, J. P. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.02.034 · Cited by 3
Nitrous Oxide-induced Impairment of Spatial Working Memory Requires Activation of GABAergic Pathways
Emmanouil, D. E., Klein, E. D., Chen, K., Brewer, A. L., Zhang, Y., & Quock, R. M. (2020) · Current Psychopharmacologye · doi:10.2174/2211556009666200217121518 · Cited by 3
Minter, R., & Gardiner, K. (2021) · Genes · doi:10.3390/genes12111697 · Cited by 2
“Here, continuous free running in the Ymaze was assessed, while i [58], the T-maze te t involved repeated si gle trials, demanding gr ater recognition of prior c oices and decision making [75].”
MethodPower of a Metabonomic Approach to Investigate an Unknown Nervous Disease
Domange, C., Paris, A., Schroeder, H., & Priymenko, N. (2011) · InTech eBooks · doi:10.5772/30963 · Cited by 3
“…tests related to locomotor activity (open-field test), motor coordination (Locotronic® apparatus, Wespoc test), learning and memory [Y maze, (Hughes, 2004), Figure 10.a and Morris water maze], anxiety [elevated plus maze, (Rodgers and Johnson, 1995), hole board (do-Rego et al., 2006;…”
BackgroundAging and the Effects of Exploratory Behavior on Spatial Memory
Varner, K. M., Dopkins, S. C., & Philbeck, J. W. (2016) · The International Journal of Aging and Human Development · doi:10.1177/0091415015626551 · Cited by 3
“Such spontaneous alternation is a welldocumented pattern in young, healthy rodents and is frequently used to examine the psychological impact of pharmacological interventions (Hughes, 2004).”
BackgroundSilva, F., Cabral, A., Lima, A., Dierschnabel, A. L., do Nascimento, E. B., Macêdo, P. T., Izídio, G. S., Ribeiro, A. M., & Silva, R. A. (2014) · Current Psychopharmacologye · doi:10.2174/22115560113026660007 · Cited by 3
“The spontaneous alternation behavior comprises the tendency for rodents and other animals to alternate their nonreinforced choices of arms in a maze at successive opportunities [40].”
BackgroundDevelopment of New Analytical Method Evaluating Working Memory on Y Maze
Gong, D.-Y., & Choi, Y. (2016) · Journal of Life Science · doi:10.5352/jls.2016.26.2.234 · Cited by 3
“여기서 자발적 교대란 하나의 통로 에 들어갔다 나올 때 다음 선택 가능한 두 개의 통로 중 이전에 탐험하지 않았던 새로운 통로를 선택하는 경우를 말하며 이는 설치류가 호기심이 많아 이전에 방문했던 통로보다는 탐험하 지 않았던 새로운 통로를 선택하는 습성을 이용한 실험법이다 [4, 8].”
Age-Dependent Cellular and Behavioral Deficits Induced by Molecularly Targeted Drugs Are Reversible
Scafidi, J., Ritter, J., Talbot, B. M., Edwards, J., Chew, L., & Gallo, V. (2018) · Cancer Research · doi:10.1158/0008-5472.can-17-2254 · Cited by 3
“The spontaneous alternation behavior is scored by determining the number of three unique arm entries (alternation) divided by the total number of arm entries minus 1 (35).”
BackgroundSichlinger, L., Reilly, M. B., Arora, S., Zhang, S., Marotta, N., Rodríguez-Acevedo, K. L., Hooks, M., Czarnecki, K. S., Winter, J. J., Waxman, E. A., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.28.685100 · Cited by 3
“We next performed Y-maze behavioral testing in adult mixed-sex mice, which provides a readout of spatial working memory unconfounded by locomotor activity 44 .”
Chen, F., Wang, H., & He, H. (2025) · Applied Physics Reviews · doi:10.1063/5.0297319 · Cited by 2
Xia, M., Wang, B., Lu, J., Liu, Y., Wang, T., Duan, J., Wang, Z., Li, L., Li, S., & Li, D. (2026) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2026.178545 · Cited by 2
Salem, H. A., Rizk, N. I., AbdelSalam, M. H., Ahmed, R., Atteia, H. H., Hamdan, A. M. E., Alghamdi, A. A., Alghusn, M. A., Alatawi, R. A., Atallah, R. A., et al. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1728908 · Cited by 2
Çaylak, E., & Maragheh, F. P. (2026) · Journal of Plant Biochemistry and Biotechnology · doi:10.1007/s13562-026-01085-9 · Cited by 2
Effect of quercetin on learning and memory in STZ-induced diabetic rat
Nasri, S., Rahimi, M., & Mozafari, M. (2014) · DOAJ (DOAJ: Directory of Open Access Journals) · Cited by 2
Paulo, S. L., Ribeiro‐Rodrigues, L., Rodrigues, R. S., Mateus, J. M., Fonseca‐Gomes, J., Soares, R., Diógenes, M. J., Solá, S., Sebastião, A. M., Ribeiro, F. F., et al. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-201567 · Cited by 2
“This test was implemented to evaluate spatial working memory performance [29, 30].”
Congenital blindness does not protect against a schizophrenia-related phenotype in rodents
Perez, S. M., Elam, H. B., McCoy, A. M., Boley, A. M., Eassa, N. E., & Lodge, D. J. (2023) · Schizophrenia Research · doi:10.1016/j.schres.2023.06.007 · Cited by 2
Metadata
- Authors
- Hughes, R. N.
- Affiliations
- University of Canterbury (NZ)
- Corresponding author
- Hughes, Robert N.
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2004-09
- Volume
- 28
- Issue
- 5
- Pages
- 497-505
- ISSN
- 0149-7634 (ISSN-L)
- OpenAlex
- W2143302321
- Cited by
- 641
- References
- 116
- Citations by year
- 2026: 37 · 2025: 47 · 2024: 38 · 2023: 39 · 2022: 54 · 2021: 45 · 2020: 55 · 2019: 41 · 2018: 35 · 2017: 38 · 2016: 28 · 2015: 18 · 2014: 26 · 2013: 24 · 2012: 24
- FWCI
- 0.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Spatial Cognition and Navigation
- Keywords
- spatial memory, memory retention, T-maze, Y-maze, responsiveness to change, drug effects on memory, attentional processes, motivation
- MeSH terms
- Acetylcholine, Animals, Attention, Behavior, Animal, Brain Chemistry, Humans, Light, Memory, Reinforcement, Psychology, Smell, Space Perception
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