A Rank-Order Procedure Applied to an Ethoexperimental Behavior Model—The Multivariate Concentric Square Field<sup>TM </sup>(MCSF) Test — Oak Academic Publishing
Research ArticleOpen AccessGoogle Scholar indexed
A Rank-Order Procedure Applied to an Ethoexperimental Behavior Model—The Multivariate Concentric Square Field<sup>TM </sup>(MCSF) Test
Department of Neuroscience, Uppsala University, Uppsala, Sweden
,
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
,
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
1 Department of Neuroscience, Uppsala University, Uppsala, Sweden
2 Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
3 Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
Designing relevant animal models in order to investigate the neurobiological basis for human mental disorders is an important challenge. The need for new tests to be developed and traditional tests to be improved has recently been em-phasized. The authors propose a multivariate test approach, the multivariate concentric square field TM (MCSF) test. To measure and evaluate variation in the behavioral traits, we here put forward a statistical procedure of which the working title is “trend analysis”. Low doses of the benzodiazepine agonist diazepam (DZP; 1.0, 1.5, or 2.0 mg/kg) were used for exploring the use of the trend analysis in combination with multivariate data analysis for assessment of MCSF per-formance in rats. The commonly used elevated plus maze (EPM) test was used for comparison. The trend analysis comparing vehicle and the DZP1.5 groups revealed significantly higher general activity and risk-taking behavior in the DZP1.5 rats relative to vehicle rats. This finding was supported by multivariate data analysis procedures. It is concluded that the trend analysis together with multivariate data analysis procedures offers possibilities to extract information and illustrates effects obtained in the MCSF test. Diazepam in doses that have no apparent increase in open arm activity in the EPM was effective to alter the behavior in the MCSF test. The MCSF test and the use of multivariate data analysis and the proposed trend analysis may be useful alternatives to behavioral test batteries and traditionally used tests for the understanding of mechanisms underlying various mental states. Finally, the impact of an ethological reasoning and multivariate measures enabling behavioral profiling of animals may be a useful complementary methodology when phenotyping animals in behavioral neuroscience.
KeywordsTrend AnalysisDiazepamElevated Plus MazeMultivariate Data Analysis
T. Nagel, “What Is It Like to Be a Bat?” The Philosophical Review, Vol. 83, No. 4, 1974, pp. 435-450. doi:10.2307/2183914
A. Miklosi, “Dog Behaviour, Evolution, and Cognition,” Oxford University Press, Oxford, 2007. doi:10.1093/acprof:oso/9780199295852.001.0001
J. F. Cryan and A. Holmes, “Model Organisms: The Ascent of Mouse: Advances in Modelling Human Depression and Anxiety,” Nature Reviews Drug Discovery, Vol. 4, 2005, pp. 775-790. doi:10.1038/nrd1825
“Anonymous, Building a Better Mouse Test,” Nature Methods, Vol. 8, 2011, p. 697. doi:10.1038/nmeth.1698
E. Fonio, I. Golani and Y. Benjamini, “Measuring Behavior of Animal Models: Faults and Remedies,” Nature Methods, Vol. 9, 2012, pp. 1167-1170. doi:10.1038/nmeth.2252
E. J. Nestler and S. E. Hyman, “Animal Models of Neuropsychiatric Disorders,” Nature Neuroscience, Vol. 13, 2010, pp. 1161-1169. doi:10.1038/nn.2647
G. Winocur, M. Moscovitch, S. Fogel, R. S. Rosenbaum and M. Sekeres, “Preserved Spatial Memory after Hippocampal Lesions: Effects of Extensive Experience in a Complex Environment,” Nature Neuroscience, Vol. 8, 2005, pp. 273-275. doi:10.1038/nn1401
A. Ennaceur, S. Michalikova, R. van Rensburg and P. L. Chazot, “Are Benzodiazepines Really Anxiolytic? Evidence from a 3D Maze Spatial Navigation Task,” Behavioural Brain Research, Vol. 188, No. 1, 2008, pp. 136-153. doi:10.1016/j.bbr.2007.10.026
A. Ramos, “Animal Models of Anxiety: Do I Need Multiple Tests?” Trends in Pharmacological Sciences, Vol. 29, No. 10, 2008, pp. 493-498. doi:10.1016/j.tips.2008.07.005
R. J. Blanchard, E. B. Yudko, R. J. Rodgers and D. C. Blanchard, “Defense System Psychopharmacology: An Ethological Approach to the Pharmacology of Fear and Anxiety,” Behavioural Brain Research, Vol. 58, No. 1-2, 1993, pp. 155-165. doi:10.1016/0166-4328(93)90100-5
B. J. Meyerson, H. Augustsson, M. Berg and E. Roman, “The Concentric Square Field: A Multivariate Test Arena for Analysis of Explorative Strategies,” Behavioural Brain Research, Vol. 168, No. 1, 2006, pp. 100-113. doi:10.1016/j.bbr.2005.10.020
D. C. Blanchard, G. Griebel and R. J. Blanchard, “The Mouse Defense Test Battery: Pharmacological and Behavioral Assays for Anxiety and Panic,” European Journal of Pharmacology, Vol. 463, No. 1-3, 2003, pp. 97-116. doi:10.1016/S0014-2999(03)01276-7
R. J. Blanchard and D. C. Blanchard, “Antipredator Defensive Behaviors in a Visible Burrow System,” Journal of Comparative Psychology, Vol. 103, No. 1, 1989, pp. 70-82. doi:10.1037/0735-7036.103.1.70
E. Roman, R. B. Stewart, M. L. Bertholomey, M. L. Jensen, G. Colombo, P. Hyytia, N. E. Badia-Elder, N. J. Grahame, T. K. Li and L. Lumeng, “Behavioral Profiling of Multiple Pairs of Rats Selectively Bred for High and Low Alcohol Intake Using the MCSF Test,” Addiction Biology, Vol. 17, No. 1, 2012, pp. 33-46. doi:10.1111/j.1369-1600.2011.00327.x
E. Roman and G. Colombo, “Lower Risk Taking and Exploratory Behavior in Alcohol-Preferring sP Rats than in Alcohol Nonpreferring sNP Rats in the Multivariate Concentric Square FieldTM (MCSF) Test,” Behavioural Brain Research, Vol. 205, No. 1, 2009, pp. 249-258. doi:10.1016/j.bbr.2009.08.020
H. Akerberg, E. Wilsson, M. Sallander, A. Hedhammar, A. L. Lagerstedt, D. Larhammar and B. Meyerson, “Test for Personality Characteristics in Dogs Used in Research,” Journal of Veterinary Behavior: Clinical Applications and Research, Vol. 7, No. 6, 2012, pp. 327-338. doi:10.1016/j.jveb.2012.01.007
K. Uekama, F. Hirayama and T. Irie, “Cyclodextrin Drug Carrier Systems,” Chemical Reviews, Vol. 98, No. 5, 1998, pp. 2045-2076. doi:10.1021/cr970025p
T. L. Yaksh, J. D. Jang, Y. Nishiuchi, K. P. Braun, S. G. Ro and M. Goodman, “The Utility of 2-Hydroxypropyl-Beta-Cyclodextrin as a Vehicle for the Intracerebral and Intrathecal Administration of Drugs,” Life Sciences, Vol. 48, No. 7, 1991, pp. 623-633. doi:10.1016/0024-3205(91)90537-L
L. Eriksson, E. Johansson, N. Kettaneh-Wold, J. Trygg, C. Wikstrom and S. Wold, “Multi and Megavariate Data Analysis. Part I: Basic Principles and Applications,” 2nd Revised and Enlarged Edition, Umetrics AB, Umea, 2006.
E. Roman, B. J. Meyerson, P. Hyytia and I. Nylander, “The Multivariate Concentric Square Field Test Reveals Different Behavioural Profiles in Male AA and ANA Rats with Regard to Risk Taking and Environmental Reactivity,” Behavioural Brain Research, Vol. 183, No. 2, 2007, pp. 195-205. doi:10.1016/j.bbr.2007.06.009
O. Karlsson, E. Roman and E. B. Brittebo, “Long-Term Cognitive Impairments in Adult Rats Treated Neonatally with {beta}-N-Methylamino-L-Alanine (BMAA),” Toxicological Sciences, Vol. 112, No. 1, 2009, pp. 185-195. doi:10.1093/toxsci/kfp196
S. J. Dahlbom, D. Lagman, K. Lundstedt-Enkel, L. F. Sundstrom and S. Winberg, “Boldness Predicts Social Status in Zebrafish (Danio rerio),” PLoS One, Vol. 6, 2011, Article ID: e23565. doi:10.1371/journal.pone.0023565
K. Lundstedt-Enkel, R. Bjerselius, L. Asplund, K. Nylund, Y. Liu and M. Sodervall, “Modeling Relationships between Baltic Sea Herring (Clupea harengus) Biology and Contaminant Concentrations Using Multivariate Data Analysis,” Environmental Science & Technology, Vol. 44, No. 23, 2010, pp. 9018-9023. doi:10.1021/es102448b
S. Palm, A. Havermark, B. J. Meyerson, I. Nylander and E. Roman, “When Is a Wistar a Wistar? Behavioral Profiling of Outbred Wistar Rats from Five Different Suppliers Using the MCSF Test,” Applied Animal Behaviour Science, Vol. 135, No. 1, 2011, pp. 128-137. doi:10.1016/j.applanim.2011.08.010
L. Daoura, M. Hjalmarsson, S. Oreland, I. Nylander and E. Roman, “Postpartum Behavioral Profiles in Wistar Rats Following Maternal Separation—Altered Exploration and Risk-Assessment Behavior in MS15 Dams,” Frontiers in Behavioral Neuroscience, Vol. 4, 2010, p. 37.
S. Ekmark-Lewen, A. Lewen, B. J. Meyerson and L. Hillered, “The Multivariate Concentric Square Field Test Reveals Behavioral Profiles of Risk Taking, Exploration, and Cognitive Impairment in Mice Subjected to Traumatic Brain Injury,” Journal of Neurotrauma, Vol. 27, No. 9, 2010, pp. 1643-1655. doi:10.1089/neu.2009.0953
G. Griebel, G. Perrault and D. J. Sanger, “Characterization of the Behavioral Profile of the Non-Peptide CRF Receptor Antagonist CP-154,526 in Anxiety Models in Rodents. Comparison with Diazepam and Buspirone,” Psychopharmacology (Berl), Vol. 138, No. 1, 1998, pp. 55-66. doi:10.1007/s002130050645
M. A. Wilson, P. R. Burghardt, K. A. Ford, M. B. Wilkinson and S. D. Primeaux, “Anxiolytic Effects of Diazepam and Ethanol in Two Behavioral Models: Comparison of Males and Females,” Pharmacology Biochemistry and Behavior, Vol. 78, No. 3, 2004, pp. 445-458. doi:10.1016/j.pbb.2004.04.017
R. Stefanski, W. Palejko, W. Kostowski and A. Plaznik, “The Comparison of Benzodiazepine Derivatives and Serotonergic Agonists and Antagonists in Two Animal Models of Anxiety,” Neuropharmacology, Vol. 31, No. 12, 1992, pp. 1251-1258. doi:10.1016/0028-3908(92)90053-R
A. O. Mechan, P. M. Moran, M. Elliott, A. J. Young, M. H. Joseph and R. Green, “A Comparison between Dark Agouti and Sprague-Dawley Rats in Their Behaviour on the Elevated Plus-Maze, Open-Field Apparatus and Activity Meters, and Their Response to Diazepam,” Psychopharmacology (Berl), Vol. 159, No. 2, 2002, pp. 188-195. doi:10.1007/s002130100902
A. A. Goepfrich, C. Gluch, C. M. Friemel and M. Schneider, “Behavioral Differences in Three Wistar Han Rat Lines for Emotional Reactivity, Cognitive Processing and Ethanol Intake,” Physiology & Behavior, Vol. 110-111, 2013, pp. 102-108. doi:10.1016/j.physbeh.2012.12.019
R. Paylor, C. M. Spencer, L. A. Yuva-Paylor and S. Pieke-Dahl, “The Use of Behavioral Test Batteries, II: Effect of Test Interval,” Physiology & Behavior, Vol. 87, No. 1, 2006, pp. 95-102. doi:10.1016/j.physbeh.2005.09.002
V. Voikar, E. Vasar and H. Rauvala, “Behavioral Alterations Induced by Repeated Testing in C57BL/6J and 129S2/Sv Mice: Implications for Phenotyping Screens,” Genes, Brain and Behavior, Vol. 3, No. 1, 2004, pp. 27-38. doi:10.1037/0735-7044.121.5.1113
S. J. Ballaz, H. Akil and S. J. Watson, “Previous Experience Affects Subsequent Anxiety-Like Responses in Rats Bred for Novelty Seeking,” Behavioral Neuroscience, Vol. 121, No. 5, 2007, pp. 1113-1118. doi:10.1037/0735-7044.121.5.1113
J. C. Crabbe, D. Wahlsten and B. C. Dudek, “Genetics of Mouse Behavior: Interactions with Laboratory Environment,” Science, Vol. 284, No. 5420, 1999, pp. 1670-1672. doi:10.1126/science.284.5420.1670
H. Augustsson, “Ethoexperimental Studies of Behaviour in Wild and Laboratory Mice. Risk Assessment, Emotional Reactivity and Animal Welfare,” Acta Universitatis Agriculturae Sueciae Veterinaria, Vol. 174, 2004, pp. 7-62.