Animal Behavior Testing in Neuroscience Research
Hande Yüceer Korkmaz, Cem İsmail KüçükaliAnimal behavior tests are widely used in neuroscience research to study the underlying mechanisms of various neurological and behavioral diseases. This section discusses the major animal behavior tests used in neuroscience research for studying anxiety, stress, depression, learning, memory, executive functions, social behavior, locomotor activity, and pain sensitivity. Anxiety is often studied using 0 maze, elevated plus maze, light dark box, open field test, and marble burying tests. Tail suspension test, the forced swim test, social defeat test, novelty suppressed feeding test, sucrose preference test, and learned helplessness test are used to measure stress and depression in animals. Further, memory and learning are typically evaluated using the Morris water maze, radial arm maze, novel object recognition test, object location memory test, active and passive avoidance tests, fear conditioning test, conditioned place preference test, T-maze, Barned maze, and Y-maze. Executive functions are commonly examined using the go/no-go task, set-shifting task, spatial reversal learning task, and multiple choice serial reaction time task. Moreover, social behavior is evaluated by social recognition test, sociability chamber, and resident-intruder test. Rotarod, open field test, beam walking test, digging test, cylinder test, wire hanging test, treadmill, and pole test are the most known tests to study locomotor activity. Lastly, pain sensitivity is evaluated using hot plate test, tail flick test, formalin test, von Frey test, and writhing tests. In conclusion, all of these tests provide important insights into the complex interplay between behavior and the brain.
Referanslar
- 1. Ericsson AC, Crim MJ, Franklin CL. A brief history of animal modeling. Mo Med. 2013;110(3):201-5. google scholar
- 2. Clark RE. The classical origins of Pavlov’s conditioning. Integr Physiol Behav Sci. 2004;39(4):279-94. google scholar
- 3. Chance P. Thorndike’s Puzzle Boxes And The Origins Of The Experimental Analysis Of Behavior. J Exp Anal Behav. 1999;72(3):433-40. google scholar
- 4. Sarter M. Animal cognition: defining the issues. Neurosci Biobehav Rev. 2004;28(7):645-50. google scholar
- 5. Harro J. Animal models of depression: pros and cons. Cell Tissue Res. 2019;377(1):5-20. google scholar
- 6. Ramos A. Animal models of anxiety: do I need multiple tests? Trends Pharmacol Sci. 2008;29(10):493-8. google scholar
- 7. Ang MJ, Lee S, Kim JC, Kim SH, Moon C. Behavioral Tasks Evaluating Schizophrenia-like Symptoms in Animal Models: A Recent Update. Curr Neuropharmacol. 2021;19(5):641-664. google scholar
- 8. Kuhn BN, Kalivas PW, Bobadilla AC. Understanding Addiction Using Animal Models. Front Behav Neurosci. 2019;13:262. google scholar
- 9. Blatchford RA. ANIMAL BEHAVIOR AND WELL-BEING SYMPOSIUM: Poultry welfare assessments: Current use and limitations. J Anim Sci. 2017;95(3):1382-1387. google scholar
- 10. Kraeuter AK, Guest PC, Sarnyai Z. The Elevated Plus Maze Test for Measuring Anxiety-Like Behavior in Rodents. Methods Mol Biol. 2019;1916:69-74. google scholar
- 11. Hu C, Luo Y, Wang H, Kuang S, Liang G, Yang Y, Mai S, Yang J. Re-evaluation of the interrela-tionships among the behavioral tests in rats exposed to chronic unpredictable mild stress. PLoS One. 2017;12(9):e0185129. google scholar
- 12. Kulkarni SK, Singh K, Bishnoi M. Elevated zero maze: a paradigm to evaluate antianxiety effects of drugs. Methods Find Exp Clin Pharmacol. 2007;29(5):343-8. google scholar
- 13. Kraeuter AK, Guest PC, Sarnyai Z. The Open Field Test for Measuring Locomotor Activity and Anxiet-y-Like Behavior. Methods Mol Biol. 2019;1916:99-103. google scholar
- 14. Sturman O, Germain PL, Bohacek J. Exploratory rearing: a context- and stress-sensitive behavior recorded in the open-field test. Stress. 2018;21(5):443-452. google scholar
- 15. Prut L, Belzung C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J Pharmacol. 2003;463(1-3):3-33. google scholar
- 16. Bourin M, Hascoet M. The mouse light/dark box test. Eur J Pharmacol. 2003;463(1-3):55-65. google scholar
- 17. Dixit PV, Sahu R, Mishra DK. Marble-burying behavior test as a murine model of compulsive-like behavior. J Pharmacol Toxicol Methods. 2020;102:106676. google scholar
- 18. Yankelevitch-Yahav R, Franko M, Huly A, Doron R. The forced swim test as a model of depressive-like behavior. J Vis Exp. 2015;(97):52587. google scholar
- 19. Commons KG, Cholanians AB, Babb JA, Ehlinger DG. The Rodent Forced Swim Test Measures Stress-Co-ping Strategy, Not Depression-like Behavior. ACS Chem Neurosci. 2017;8(5):955-960. google scholar
- 20. Cryan JF, Mombereau C, Vassout A. The tail suspension test as a model for assessing antidepressant acti-vity: review of pharmacological and genetic studies in mice. Neurosci Biobehav Rev. 2005;29(4-5):571-625. google scholar
- 21. Iniguez SD, Riggs LM, Nieto SJ, Dayrit G, Zamora NN, Shawhan KL, Cruz B, Warren BL. Social defeat stress induces a depression-like phenotype in adolescent male c57BL/6 mice. Stress. 2014;17(3):247-55. google scholar
- 22. Blasco-Serra A, Gonzalez-Soler EM, Cervera-Ferri A, Teruel-Marti V, Valverde-Navarro AA. A standar-dization of the Novelty-Suppressed Feeding Test protocol in rats. Neurosci Lett. 2017;658:73-78. Fang X, Jiang S, Wang J, Bai Y, Kim CS, Blake D, Weintraub NL, Lei Y, Lu XY. Chronic unpredictab-le stress induces depression-related behaviors by suppressing AgRP neuron activity. Mol Psychiatry. 2021;26(6):2299-2315. google scholar
- 23. Liu MY, Yin CY, Zhu LJ, Zhu XH, Xu C, Luo CX, Chen H, Zhu DY, Zhou QG. Sucrose preference test for measurement of stress-induced anhedonia in mice. Nat Protoc. 2018;13(7):1686-1698. google scholar
- 24. Yan HC, Cao X, Das M, Zhu XH, Gao TM. Behavioral animal models of depression. Neurosci Bull. 2010;26(4):327-37. google scholar
- 25. Schöner J, Heinz A, Endres M, Gertz K, Kronenberg G. Post-traumatic stress disorder and beyond: an overview of rodent stress models. J Cell Mol Med. 2017;21(10):2248-2256. google scholar
- 26. Hölter SM, Garrett L, Einicke J, Sperling B, Dirscherl P, Zimprich A, Fuchs H, Gailus-Durner V, Hrabe de Angelis M, Wurst W. Assessing Cognition in Mice. Curr Protoc Mouse Biol. 2015;5(4):331-358. google scholar
- 27. Othman MZ, Hassan Z, Che Has AT. Morris water maze: a versatile and pertinent tool for assessing spatial learning and memory. Exp Anim. 2022;71(3):264-280. google scholar
- 28. Bromley-Brits K, Deng Y, Song W. Morris water maze test for learning and memory deficits in Alzheimer’s disease model mice. J Vis Exp. 2011;(53):2920. google scholar
- 29. Hodges H. Maze procedures: the radial-arm and water maze compared. Brain Res Cogn Brain Res. 1996 Jun;3(3-4):167-81. google scholar
- 30. Matsuoka N, Maeda N, Yamazaki M, Ohkubo Y, Yamaguchi I. Effect of FR121196, a novel cognitive enhancer, on the memory impairment of rats in passive avoidance and radial arm maze tasks. J Pharmacol Exp Ther. 1992;263(2):436-44. google scholar
- 31. Lueptow LM. Novel Object Recognition Test for the Investigation of Learning and Memory in Mice. J Vis Exp. 2017;(126):55718. google scholar
- 32. Grayson B, Leger M, Piercy C, Adamson L, Harte M, Neill JC. Assessment of disease-related cognitive impairments using the novel object recognition (NOR) task in rodents. Behav Brain Res. 2015;285:176-93. google scholar
- 33. Denninger JK, Smith BM, Kirby ED. Novel Object Recognition and Object Location Behavioral Testing in Mice on a Budget. J Vis Exp. 2018;(141):10.3791/58593. google scholar
- 34. Cimadevilla JM, Kaminsky Y, Fenton A, Bures J. Passive and active place avoidance as a tool of spatial memory research in rats. J Neurosci Methods. 2000;102(2):155-64. google scholar
- 35. Kuboyama K, Shirakawa Y, Kawada K, Fujii N, Ojima D, Kishimoto Y, Yamamoto T, Yamada MK. Visual-ly cued fear conditioning test for memory impairment related to cortical function. Neuropsychopharmacol Rep. 2020;40(4):371-375. google scholar
- 36. Shoji H, Takao K, Hattori S, Miyakawa T. Contextual and cued fear conditioning test using a video anal-yzing system in mice. J Vis Exp. 2014;(85):50871. google scholar
- 37. Scherma M, Fattore L, Fratta W, Fadda P. Conditioned Place Preference (CPP) in Rats: From Conditioning to Reinstatement Test. Methods Mol Biol. 2021;2201:221-229. google scholar
- 38. Marion-Poll L, Besnard A, Longueville S, Valjent E, Engmann O, Caboche J, Herve D, Girault JA. Cocaine conditioned place preference: unexpected suppression of preference due to testing combined with strong conditioning. Addict Biol. 2019;24(3):364-375. google scholar
- 39. Wu X, Zhao N, Bai F, Li C, Liu C, Wei J, Zong W, Yang L, Ryabinin AE, Ma Y, Wang J. Morphine-indu-ced conditioned place preference in rhesus monkeys: Resistance to inactivation of insula and extinction. Neurobiol Learn Mem. 2016;131:192-200. google scholar
- 40. Mathur P, Lau B, Guo S. Conditioned place preference behavior in zebrafish. Nat Protoc. 2011;6(3):338-45. google scholar
- 41. Deacon RM, Rawlins JN. T-maze alternation in the rodent. Nat Protoc. 2006;1(1):7-12. google scholar
- 42. Marin RH, Satterlee DG, Cadd GG, Jonest RB. T-maze behavior and early egg production in Japanese quail selected for contrasting adrenocortical responsiveness. Poult Sci. 2002;81(7):981-6. google scholar
- 43. Ngoc Hieu BT, Ngoc Anh NT, Audira G, Juniardi S, Liman RAD, Villaflores OB, Lai YH, Chen JR, Liang ST, Huang JC, Hsiao CD. Development of a Modified Three-Day T-maze Protocol for Evaluating Learning and Memory Capacity of Adult Zebrafish. Int J Mol Sci. 2020;21(4):1464. google scholar
- 44. Pitts MW. Barnes Maze Procedure for Spatial Learning and Memory in Mice. Bio Protoc. 2018;8(5):e2744. google scholar
- 45. Attar A, Liu T, Chan WT, Hayes J, Nejad M, Lei K, Bitan G. A shortened Barnes maze protocol reveals memory deficits at 4-months of age in the triple-transgenic mouse model of Alzheimer’s disease. PLoS One. 2013;8(11):e80355. google scholar
- 46. Kraeuter AK, Guest PC, Sarnyai Z. The Y-Maze for Assessment of Spatial Working and Reference Memory in Mice. Methods Mol Biol. 2019;1916:105-111. google scholar
- 47. Talpos J, Shoaib M. Executive function. Handb Exp Pharmacol. 2015;228:191-213. google scholar
- 48. Cole E, Chad M, Moman V, Mumby DG. A Go/No-go delayed nonmatching-to-sample procedure to measure object-recognition memory in rats. Behav Processes. 2020;178:104180. google scholar
- 49. Tait DS, Bowman EM, Neuwirth LS, Brown VJ. Assessment of intradimensional/extradimensional atten-tional set-shifting in rats. Neurosci Biobehav Rev. 2018;89:72-84. google scholar
- 50. Magara F, Boury-Jamot B, Hörnberg H. A Simple Spatial-independent Associative and Reversal Learning Task in Mice. Bio Protoc. 2021;11(15):e4108. google scholar
- 51. Amitai N, Markou A. Disruption of performance in the five-choice serial reaction time task induced by administration of N-methyl-D-aspartate receptor antagonists: relevance to cognitive dysfunction in schi-zophrenia. Biol Psychiatry. 2010;68(1):5-16. google scholar
- 52. Tanaka M, Kunugi A, Suzuki A, Suzuki N, Suzuki M, Kimura H. Preclinical characterization of AMPA receptor potentiator TAK-137 as a therapeutic drug for schizophrenia. Pharmacol Res Perspect. 2019;7(3):e00479. google scholar
- 53. Venerosi A, Calamandrei G, Ricceri L. A social recognition test for female mice reveals behavioral effects of developmental chlorpyrifos exposure. Neurotoxicol Teratol. 2006;28(4):466-71. google scholar
- 54. Hodges TE, Baumbach JL, Marcolin ML, Bredewold R, Veenema AH, McCormick CM. Social instability stress in adolescent male rats reduces social interaction and social recognition performance and increases oxytocin receptor binding. Neuroscience. 2017;359:172-182. google scholar
- 55. Kaidanovich-Beilin O, Lipina T, Vukobradovic I, Roder J, Woodgett JR. Assessment of social interaction behaviors. J Vis Exp. 2011;(48):2473. google scholar
- 56. Moy SS, Nadler JJ, Perez A, Barbaro RP, Johns JM, Magnuson TR, Piven J, Crawley JN. Sociability and preference for social novelty in five inbred strains: an approach to assess autistic-like behavior in mice. Genes Brain Behav. 2004;3(5):287-302. google scholar
- 57. Kordas K, Kis-Varga A, Varga A, Eldering H, Bulthuis R, Lendvai B, Levay G, Roman V. Measuring sociability of mice using a novel three-chamber apparatus and algorithm of the LABORAS™ system. J Neurosci Methods. 2020;343:108841. google scholar
- 58. Koolhaas JM, Coppens CM, de Boer SF, Buwalda B, Meerlo P, Timmermans PJ. The resident-intruder paradigm: a standardized test for aggression, violence and social stress. J Vis Exp. 2013;(77):e4367. google scholar
- 59. Tosini G. Locomotor activity in rodents. Methods Mol Biol. 2007;362:95-101. google scholar
- 60. Shiotsuki H, Yoshimi K, Shimo Y, Funayama M, Takamatsu Y, Ikeda K, Takahashi R, Kitazawa S, Hattori N. A rotarod test for evaluation of motor skill learning. J Neurosci Methods. 2010;189(2):180-5. google scholar
- 61. Antiorio AT, Aleman-Laporte J, Zanatto DA, Pereira MAA, Gomes MS, Wadt D, Yamamoto PK, Bernardi MM, Mori CM. Mouse Behavior in the Open-field Test after Meloxicam Administration. J Am Assoc Lab Anim Sci. 2022;61(3):270-274. google scholar
- 62. Carter RJ, Morton J, Dunnett SB. Motor coordination and balance in rodents. Curr Protoc Neurosci. 2001;Chapter 8:Unit 8.12. google scholar
- 63. Pond HL, Heller AT, Gural BM, McKissick OP, Wilkinson MK, Manzini MC. Digging behavior disc-rimination test to probe burrowing and exploratory digging in male and female mice. J Neurosci Res. 2021;99(9):2046-2058. google scholar
- 64. Magno LAV, Collodetti M, Tenza-Ferrer H, Romano-Silva MA. Cylinder Test to Assess Sensory-motor Function in a Mouse Model of Parkinson’s Disease. Bio Protoc. 2019;9(16):e3337. google scholar
- 65. Hoffman E, Winder SJ. A Modified Wire Hanging Apparatus for Small Animal Muscle Function Testing. PLoS Curr. 2016;8. google scholar
- 66. Hadadianpour Z, Fatehi F, Ayoobi F, Kaeidi A, Shamsizadeh A, Fatemi I. The effect of orexin-A on motor and cognitive functions in a rat model of Parkinson’s disease. Neurol Res. 2017;39(9):845-851. google scholar
- 67. Wooley CM, Xing S, Burgess RW, Cox GA, Seburn KL. Age, experience and genetic background influence treadmill walking in mice. Physiol Behav. 2009;96(2):350-61. google scholar
- 68. Ruan J, Yao Y. Behavioral tests in rodent models of stroke. Brain Hemorrhages. 2020;1(4):171-184. google scholar
- 69. Li R, Chen J. Salidroside Protects Dopaminergic Neurons by Enhancing PINK1/Parkin-Mediated Mitop-hagy. Oxid Med Cell Longev. 2019;2019:9341018. google scholar
- 70. Kedaigle AJ, Reidling JC, Lim RG, Adam M, Wu J, Wassie B, Stocksdale JT, Casale MS, Fraenkel E, Thompson LM. Treatment with JQ1, a BET bromodomain inhibitor, is selectively detrimental to R6/2 Huntington’s disease mice. Hum Mol Genet. 2020;29(2):202-215. google scholar
- 71. Balkaya M, Kröber J, Gertz K, Peruzzaro S, Endres M. Characterization of long-term functional outcome in a murine model of mild brain ischemia. J Neurosci Methods. 2013;213(2):179-87. google scholar
- 72. Bannon AW, Malmberg AB. Models of nociception: hot-plate, tail-flick, and formalin tests in rodents. Curr Protoc Neurosci. 2007;Chapter 8:Unit 8.9. google scholar
- 73. Bannon AW. Models of pain: hot-plate and formalin test in rodents. Curr Protoc Pharmacol. 2001;Chapter 5:Unit 5.7. google scholar
- 74. Deuis JR, Dvorakova LS, Vetter I. Methods Used to Evaluate Pain Behaviors in Rodents. Front Mol Neurosci. 2017;10:284. google scholar
- 75. Naghizadeh B, Mansouri MT, Ghorbanzadeh B. Ellagic acid enhances the antinociceptive action of carba-mazepine in the acetic acid writhing test with mice. Pharm Biol. 2016;54(1):157-61. google scholar
- 76. Valls-Sole J. Prepulse inhibition on the spot. Clin Neurophysiol. 2021;132(10):2679-2680. google scholar
- 77. Naysmith LF, Kumari V, Williams SCR. Neural mapping of prepulse-induced startle reflex modulation as indices of sensory information processing in healthy and clinical populations: A systematic review. Hum Brain Mapp. 2021;42(16):5495-5518. google scholar
- 78. Oral S, Göktalay G. Prepulse inhibition based grouping of rats and assessing differences in response to pharmacological agents. Neurosci Lett. 2021;755:135913. google scholar
- 79. Ioannidou C, Marsicano G, Busquets-Garcia A. Assessing Prepulse Inhibition of Startle in Mice. Bio Protoc. 2018;8(7):e2789. google scholar
- 80. Akhtar A. The flaws and human harms of animal experimentation. Camb Q Healthc Ethics. 2015;24(4):407-19. google scholar