Behavioral Tests Used in Experimental Animal Models

Year 2022, Volume: 3 Issue: 2, 14 - 22, 31.12.2022

Mehmet Ali Yörük Ufuk Okkay Ayşenur Budak Savaş Cemil Bayram Selma Sezen Muhammed Sait Ertuğrul Ahmet Hacımüftüoğlu

Abstract

Experimental animals are used to develop treatments for diseases in humans and animals and to control pathophysiological processes. Biochemical and pathological parameters are still insufficient to explain behavioral disorders. Therefore, behavioral models are necessary to understand the pathophysiology of diseases and accelerate the development of treatments. Experimental animal models show the clinical reflection of many purposes such as drug research for diseases, toxicity of drugs and prevention of toxicity, understanding drug effects, understanding biological processes in diseases. Although data from behavioral models can be evaluated using a single test, it is more efficient to use a set of tests consisting of different tests that show traits on the behavioral phenotype. In this study, Elevated plus maze, Passive avoidence, Locomotor activity, Fear conditioning, Morris water maze, Randall Selitto paw pressure, Von Frey, Forced swim and Apomorphine induced rotation tests, which are widely used in neurological studies in mouse and rat species, are explained. In addition, it is mentioned for what purpose the specified behavior models are used. In this review, important behavioral models commonly used in neurological studies measure which parameter, their procedures and goals, and some of the animal- and environmental-related factors that affect behavior.

Keywords

Behavioral test, Neurodegeneration, Animal model, Anxiety, Depression

References

• J. S. Mogil, "Animal models of pain: progress and challenges," Nat Rev Neurosci, vol. 10, no. 4, pp. 283-94, Apr 2009, doi: 10.1038/nrn2606.
• N. E. Burma, H. Leduc-Pessah, C. Y. Fan, and T. Trang, "Animal models of chronic pain: Advances and challenges for clinical translation," J Neurosci Res, vol. 95, no. 6, pp. 1242-1256, Jun 2017, doi: 10.1002/jnr.23768.
• C. Bayram and A. Hacimuftuoglu, "Investigation of Antioxidant Efficacy of Glycyrrhiza glabra L. Extract in Glutamate Toxicity-Induced Primary Neuron Culture," Anatol. j. bio., vol. 3, no. 1, pp. 18-24, 2022.
• A. Hacımüftüoğlu, U. Okkay, M. Sağsöz, and M. Taşpınar, "Deneysel Alzheimer Modelinde Hipokampüste Glutamat Geri Alınım Parametrelerinin Değerlendirilmesi," in Nöropsikiyatriye ve Ağrıya Multidisipliner Yaklaşım, Ü. Atilan Fedağ Ed.: IKSAD Yayınları, 2021, pp. 3-18.
• S. Sezen, M. Isaoğlu, M. Güllüce, M. Karadayi, G. Karadayi, N.H. Ispirli, V. Yildirim, " Genotoxicity Evaluation of the Vitex agnus-castus L. Essential Oil with the Yeast DEL Assay," IJSER, Vol. 10, Issue 9, pp. 14-17, Sep 2019.
• U. Okkay, I. Ferah Okkay, B. Cicek, I. C. Aydin, and M. Ozkaraca, "Hepatoprotective and neuroprotective effect of taxifolin on hepatic encephalopathy in rats," Metab Brain Dis, vol. 37, no. 5, pp. 1541-1556, Jun 2022, doi: 10.1007/s11011-022-00952-3.
• Z. Rabiei, M. Hojjati, M. Rafieian-Kopaeia, and Z. Alibabaei, "Effect of Cyperus rotundus tubers ethanolic extract on learning and memory in animal model of Alzheimer," Biomed. Aging Pathol., vol. 3, no. 4, pp. 185-191, 2013.
• M. Amani, M. Zolghadrnasab, and A. A. Salari, "NMDA receptor in the hippocampus alters neurobehavioral phenotypes through inflammatory cytokines in rats with sporadic Alzheimer-like disease," (in English), Physiol Behav, vol. 202, pp. 52-61, Apr 1, 2019, doi: 10.1016/j.physbeh.2019.01.005.
• M. Calvo, J. M. Dawes, and D. L. Bennett, "The role of the immune system in the generation of neuropathic pain," Lancet Neurol, vol. 11, no. 7, pp. 629-42, Jul 2012, doi: 10.1016/S1474-4422(12)70134-5.
• H. S. Choi et al., "PEP-1-SOD fusion protein efficiently protects against paraquat-induced dopaminergic neuron damage in a Parkinson disease mouse model," Free Radic Biol Med, vol. 41, no. 7, pp. 1058-68, Oct 1 2006, doi: 10.1016/j.freeradbiomed.2006.06.006.
• D. J. Stein and R. M. Nesse, "Threat detection, precautionary responses, and anxiety disorders," Neurosci Biobehav Rev, vol. 35, no. 4, pp. 1075-9, Mar 2011, doi: 10.1016/j.neubiorev.2010.11.012.
• P. C. Hart et al., "Experimental models of anxiety for drug discovery and brain research," Methods Mol Biol, vol. 602, pp. 299-321, 2010, doi: 10.1007/978-1-60761-058-8_18.
• J. P. Curley, V. Rock, A. M. Moynihan, P. Bateson, E. B. Keverne, and F. A. Champagne, "Developmental shifts in the behavioral phenotypes of inbred mice: the role of postnatal and juvenile social experiences," Behav Genet, vol. 40, no. 2, pp. 220-32, Mar 2010, doi: 10.1007/s10519-010-9334-4.
• J. Simpson and J. P. Kelly, "The impact of environmental enrichment in laboratory rats--behavioural and neurochemical aspects," Behav Brain Res, vol. 222, no. 1, pp. 246-64, Sep 12 2011, doi: 10.1016/j.bbr.2011.04.002.
• N. I. H. A. R. Committee, Using Animals in Intramural Research: Guidelines for Investigators and Guidelines for Animal Users. NIH Animal Research Advisory Committee, NIH Office of Animal Care and Use, 2000.
• R. M. Deacon, "Housing, husbandry and handling of rodents for behavioral experiments," Nat Protoc, vol. 1, no. 2, pp. 936-46, 2006, doi: 10.1038/nprot.2006.120.
• A. Sale, N. Berardi, and L. Maffei, "Enrich the environment to empower the brain," Trends Neurosci, vol. 32, no. 4, pp. 233-9, Apr 2009, doi: 10.1016/j.tins.2008.12.004.
• G. Z. Reus et al., "Maternal deprivation induces depressive-like behaviour and alters neurotrophin levels in the rat brain," Neurochem Res, vol. 36, no. 3, pp. 460-6, Mar 2011, doi: 10.1007/s11064-010-0364-3.
• L. Petrosini et al., "On whether the environmental enrichment may provide cognitive and brain reserves," Brain Res Rev, vol. 61, no. 2, pp. 221-39, Oct 2009, doi: 10.1016/j.brainresrev.2009.07.002.
• Y. Pena, M. Prunell, D. Rotllant, A. Armario, and R. M. Escorihuela, "Enduring effects of environmental enrichment from weaning to adulthood on pituitary-adrenal function, pre-pulse inhibition and learning in male and female rats," Psychoneuroendocrinology, vol. 34, no. 9, pp. 1390-404, Oct 2009, doi: 10.1016/j.psyneuen.2009.04.019.
• J. W. Jahng, J. G. Kim, H. J. Kim, B. T. Kim, D. W. Kang, and J. H. Lee, "Chronic food restriction in young rats results in depression- and anxiety-like behaviors with decreased expression of serotonin reuptake transporter," Brain Res, vol. 1150, pp. 100-7, May 30 2007, doi: 10.1016/j.brainres.2007.02.080.
• K. Wager-Smith and A. Markou, "Depression: a repair response to stress-induced neuronal microdamage that can grade into a chronic neuroinflammatory condition?," Neurosci Biobehav Rev, vol. 35, no. 3, pp. 742-764, 2011.
• S. Morley-Fletcher et al., "Chronic agomelatine treatment corrects behavioral, cellular, and biochemical abnormalities induced by prenatal stress in rats," Psychopharmacology (Berl), vol. 217, no. 3, pp. 301-13, Oct 2011, doi: 10.1007/s00213-011-2280-x.
• A. Fornito, A. Zalesky, and M. Breakspear, "The connectomics of brain disorders," Nat Rev Neurosci, vol. 16, no. 3, pp. 159-72, Mar 2015, doi: 10.1038/nrn3901.
• J. Cordoba, "New assessment of hepatic encephalopathy," J Hepatol, vol. 54, no. 5, pp. 1030-40, May 2011, doi: 10.1016/j.jhep.2010.11.015.
• B. J. He, A. Z. Snyder, J. L. Vincent, A. Epstein, G. L. Shulman, and M. Corbetta, "Breakdown of functional connectivity in frontoparietal networks underlies behavioral deficits in spatial neglect," Neuron, vol. 53, no. 6, pp. 905-18, Mar 15 2007, doi: 10.1016/j.neuron.2007.02.013.
• T. Steimer, "Animal models of anxiety disorders in rats and mice: some conceptual issues," Dialogues Clin. Neurosci., vol. 13, no. 4, pp. 495-506, Dec 2011, doi: 10.31887/DCNS.2011.13.4/tsteimer
• S. L. Handley and S. Mithani, "Effects of alpha-adrenoceptor agonists and antagonists in a maze-exploration model of 'fear'-motivated behaviour," Naunyn Schmiedebergs Arch Pharmacol, vol. 327, no. 1, pp. 1-5, Aug 1984, doi: 10.1007/BF00504983.
• S. Pellow and S. E. File, "Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: a novel test of anxiety in the rat," Pharmacol Biochem Behav, vol. 24, no. 3, pp. 525-529, Mar 1986, doi: 10.1016/0091-3057(86)90552-6.
• A. A. Walf and C. A. Frye, "The use of the elevated plus maze as an assay of anxiety-related behavior in rodents," (in English), Nat Protoc, vol. 2, no. 2, pp. 322-328, 2007, doi: 10.1038/nprot.2007.44.
• V. Gimenez De Bejar, M. Caballero Bleda, N. Popovic, and M. Popovic, "Verapamil Blocks Scopolamine Enhancement Effect on Memory Consolidation in Passive Avoidance Task in Rats," Front Pharmacol, vol. 8, p. 566, 2017, doi: 10.3389/fphar.2017.00566.
• N. Hosseini, H. Alaei, P. Reisi, and M. Radahmadi, "The effect of treadmill running on passive avoidance learning in animal model of Alzheimer disease," International journal of preventive medicine, vol. 4, no. 2, pp. 187-192, 2012.
• C. Wu et al., "Effects of Exercise Training on Anxious-Depressive-like Behavior in Alzheimer Rat," Med Sci Sports Exerc, vol. 52, no. 7, pp. 1456-1469, Jul 2020, doi: 10.1249/MSS.0000000000002294.
• M. A. Erdogan, M. Kirazlar, G. Yigitturk, and O. Erbas, "Digoxin Exhibits Neuroprotective Properties in a Rat Model of Dementia," Neurochem Res, vol. 47, no. 5, pp. 1290-1298, May 2022, doi: 10.1007/s11064-022-03528-w.
• Z. Liu, M. Kumar, and A. Kabra, "Cucurbitacin B exerts neuroprotection in a murine Alzheimer's disease model by modulating oxidative stress, inflammation, and neurotransmitter levels," Front Biosci (Landmark Ed), vol. 27, no. 2, p. 71, Feb 17 2022, doi: 10.31083/j.fbl2702071.
• Y. Lu et al., "Neuron-Derived Estrogen Regulates Synaptic Plasticity and Memory," J Neurosci, vol. 39, no. 15, pp. 2792-2809, Apr 10 2019, doi: 10.1523/JNEUROSCI.1970-18.2019.
• M. Alsalem et al., "Impairment in locomotor activity as an objective measure of pain and analgesia in a rat model of osteoarthritis," (in English), Exp Ther Med, vol. 20, no. 6, p. 165, Dec 2020, doi: 10.3892/etm.2020.9294.
• J. P. Johansen, C. K. Cain, L. E. Ostroff, and J. E. LeDoux, "Molecular mechanisms of fear learning and memory," Cell, vol. 147, no. 3, pp. 509-524, Oct 28 2011, doi: 10.1016/j.cell.2011.10.009.
• L. H. Jacobson and J. F. Cryan, "Genetic approaches to modeling anxiety in animals," Behavioral neurobiology of anxiety and its treatment, pp. 161-201, 2009.
• T. Inoue, Y. Kitaichi, and T. Koyama, "SSRIs and conditioned fear," Prog Neuropsychopharmacol Biol Psychiatry, vol. 35, no. 8, pp. 1810-1819, Dec 1 2011, doi: 10.1016/j.pnpbp.2011.09.002.
• A. C. Campos, M. V. Fogaca, D. C. Aguiar, and F. S. Guimaraes, "Animal models of anxiety disorders and stress," Braz J Psychiatry, vol. 35 Suppl 2, pp. 101-111, 2013, doi: 10.1590/1516-4446-2013-1139.
• R. D'Hooge and P. P. De Deyn, "Applications of the Morris water maze in the study of learning and memory," Brain Res Brain Res Rev, vol. 36, no. 1, pp. 60-90, Aug 2001, doi: 10.1016/s0165-0173(01)00067-4.
• G. Ramirez, E. A. Gunderson, S. C. Levine, and S. L. Beilock, "Spatial anxiety relates to spatial abilities as a function of working memory in children," (in English), Q J Exp Psychol, vol. 65, no. 3, pp. 474-487, 2012, doi: 10.1080/17470218.2011.616214.
• J. N. Crawley, "Behavioral phenotyping strategies for mutant mice," Neuron, vol. 57, no. 6, pp. 809-818, Mar 27 2008, doi: 10.1016/j.neuron.2008.03.001.
• S. Olkun and A. Altun, "İlköğretim öğrencilerinin bilgisayar deneyimleri ile uzamsal düşünme ve geometri başarıları arasındaki ilişki," Turkish Online J. Educ. Technol., vol. 2, no. 4, pp. 86-91, 2003.
• D. Yang et al., "Developmental exposure to polychlorinated biphenyls interferes with experience-dependent dendritic plasticity and ryanodine receptor expression in weanling rats," Environ Health Perspect, vol. 117, no. 3, pp. 426-435, Mar 2009, doi: 10.1289/ehp.11771.
• C. T. Cross, T. A. Woods, and H. E. Schweingruber, Mathematics learning in early childhood: Paths toward excellence and equity. Washington, USA: National Academies Press, 2009, https://doi.org/10.17226/12519.
• M. S. Alavi, S. Fanoudi, M. Hosseini, and H. R. Sadeghnia, "Beneficial effects of levetiracetam in streptozotocin-induced rat model of Alzheimer's disease," Metab Brain Dis, vol. 37, no. 3, pp. 689-700, Mar 2022, doi: 10.1007/s11011-021-00888-0.
• N. A. Noor et al., "Effect of curcumin nanoparticles on streptozotocin-induced male Wistar rat model of Alzheimer's disease," Metab Brain Dis, vol. 37, no. 2, pp. 343-357, Feb 2022, doi: 10.1007/s11011-021-00897-z.
• A. P. Moreira et al., "The Methylglyoxal/RAGE/NOX-2 Pathway is Persistently Activated in the Hippocampus of Rats with STZ-Induced Sporadic Alzheimer's Disease," (in English), Neurotox Res, vol. 40, no. 2, pp. 395-409, Apr 2022, doi: 10.1007/s12640-022-00476-9.
• A. S. Jaggi, V. Jain, and N. Singh, "Animal models of neuropathic pain," Fundam Clin Pharmacol, vol. 25, no. 1, pp. 1-28, Feb 2011, doi: 10.1111/j.1472-8206.2009.00801.x.
• N. S. Gregory, A. L. Harris, C. R. Robinson, P. M. Dougherty, P. N. Fuchs, and K. A. Sluka, "An overview of animal models of pain: disease models and outcome measures," J Pain, vol. 14, no. 11, pp. 1255-1269, Nov 2013, doi: 10.1016/j.jpain.2013.06.008.
• B. Tena, B. Escobar, M. J. Arguis, C. Cantero, J. Rios, and C. Gomar, "Reproducibility of Electronic Von Frey and Von Frey monofilaments testing," Clin J Pain, vol. 28, no. 4, pp. 318-323, May 2012, doi: 10.1097/AJP.0b013e31822f0092.
• M. Fidanboylu, L. A. Griffiths, and S. J. Flatters, "Global inhibition of reactive oxygen species (ROS) inhibits paclitaxel-induced painful peripheral neuropathy," PLoS One, vol. 6, no. 9, p. e25212, 2011, doi: 10.1371/journal.pone.0025212.
• R. Yankelevitch-Yahav, M. Franko, A. Huly, and R. Doron, "The forced swim test as a model of depressive-like behavior," (in English), Jove-J Vis Exp, no. 97, p. e52587, Mar 2 2015, doi: 10.3791/52587.
• B. Czéh, E. Fuchs, O. Wiborg, and M. Simon, "Animal models of major depression and their clinical implications," Prog. Neuropsychopharmacol. Biol. Psychiatry, vol. 64, pp. 293-310, 2016.
• R. D. Porsolt, M. Le Pichon, and M. Jalfre, "Depression: a new animal model sensitive to antidepressant treatments," Nature, vol. 266, no. 5604, pp. 730-732, Apr 21 1977, doi: 10.1038/266730a0.
• V. Krishnan and E. J. Nestler, "Animal models of depression: molecular perspectives," Curr Top Behav Neurosci, vol. 7, pp. 121-147, 2011, doi: 10.1007/7854_2010_108.
• K. Miyanishi et al., "Behavioral tests predicting striatal dopamine level in a rat hemi-Parkinson's disease model," Neurochem Int, vol. 122, pp. 38-46, Jan 2019, doi: 10.1016/j.neuint.2018.11.005.
• U. Ungerstedt, "Postsynaptic supersensitivity after 6-hydroxy-dopamine induced degeneration of the nigro-striatal dopamine system," Acta Physiol Scand Suppl, vol. 367, no. 367, pp. 69-93, 1971, doi: 10.1111/j.1365-201x.1971.tb11000.x.
• H. Boraci, O. Kirazli, R. Gulhan, D. Yildiz Sercan, and U. S. Sehirli, "Neuroprotective effect of regular swimming exercise on calretinin-positive striatal neurons of Parkinsonian rats," Anat Sci Int, vol. 95, no. 4, pp. 429-439, Sep 2020, doi: 10.1007/s12565-020-00538-y.