Effect of Enrichment Devices on Aggression in Manipulated Nude Mice.

Agonistic behavior in group-housed male mice is a recurring problem in many animal research facilities. Common management procedures, such as the removal of aggressors, are moderately successful but often fail, owing to recurrence of aggressive behavior among cagemates. Studies have incorporated enrichment devices to attenuate aggression, but such devices have had mixed results. However, these studies did not include research manipulations when assessing the benefits of various enrichment devices. We obtained 100 male athymic nude mice and studied the efficacy of various enrichment devices, including cotton squares, paper rolls, shredded paper, nylon bones, and a mouse house and wheel combination in the reduction of fighting during an ongoing study that involved randomization followed by prostate and intratibial injections. Groups were evaluated according to a numerical grading system for wound assessment. Examination of the data revealed that the enrichment devices had no effect on the presence of wounds, thus none of the devices tested affected fighting in nude mice. However, when mice began experimental use, fight wounds increased significantly at cage change and after randomization, reflecting a disruption of existing social hierarchies. Therefore, in the context of an actual research study that involves common manipulations, the specific enrichment device had less effect on aggression in male nude mice than did the destruction and reconstruction of social structures within each group.

[1]  Lloyd H. Michael,et al.  The Guide for the Care and Use of Laboratory Animals. , 2016, ILAR journal.

[2]  H. Würbel,et al.  The impact of environmental enrichment on the outcome variability and scientific validity of laboratory animal studies. , 2014, Revue scientifique et technique.

[3]  Kathleen Pritchett-Corning,et al.  The time-to-integrate-to-nest test as an indicator of wellbeing in laboratory mice. , 2014, Journal of the American Association for Laboratory Animal Science : JAALAS.

[4]  R. Canese,et al.  The Directive 2010/63/EU on animal experimentation may skew the conclusions of pharmacological and behavioural studies , 2013, Scientific Reports.

[5]  T. Mackay,et al.  Genetics of aggression. , 2012, Annual review of genetics.

[6]  J. Papadopoulos,et al.  Targeted antivascular therapy with the apolipoprotein(a) kringle V, rhLK8, inhibits the growth and metastasis of human prostate cancer in an orthotopic nude mouse model. , 2012, Neoplasia.

[7]  L. Toth,et al.  Environmental enrichment of laboratory rodents: the answer depends on the question. , 2011, Comparative medicine.

[8]  Christie P. Karpiak,et al.  Separating the effects of shelter from additional cage enhancements for group-housed BALB/cJ mice , 2011, Neuroscience Letters.

[9]  U. Abou-Ismail.  The effects of cage enrichment on agonistic behaviour and dominance in male laboratory rats (Rattus norvegicus). , 2011, Research in veterinary science.

[10]  E. Kravitz,et al.  A single social defeat reduces aggression in a highly aggressive strain of Drosophila , 2010, Proceedings of the National Academy of Sciences.

[11]  J. Balcombe.  Laboratory Rodent Welfare: Thinking Outside the Cage , 2010, Journal of applied animal welfare science : JAAWS.

[12]  S. Moy,et al.  Effects of cage size and enrichment on reproductive performance and behavior in C57BL/6Tac mice , 2009, Lab Animal.

[13]  J. Garner,et al.  Effects of a running wheel-igloo enrichment on aggression, hierarchy linearity, and stereotypy in group-housed male CD-1 (ICR) mice , 2008 .

[14]  V. Baumans,et al.  The Influence of the Location of a Nest Box in an Individually Ventilated Cage on the Preference of Mice to Use It , 2007, Journal of applied animal welfare science : JAAWS.

[15]  J. Gonder,et al.  A renewed look at laboratory rodent housing and management. , 2007, ILAR journal.

[16]  Joseph P. Garner,et al.  Refinement of rodent research through environmental enrichment and systematic randomization , 2007 .

[17]  H. Würbel.  Environmental enrichment does not disrupt standardisation of animal experiments. , 2007, ALTEX.

[18]  J. Balcombe,et al.  Laboratory environments and rodents' behavioural needs: a review , 2006, Laboratory animals.

[19]  E. Kaliste,et al.  Environmental modification and agonistic behavior in NIH/S male mice: nesting material enhances fighting but shelters prevent it. , 2006, Comparative medicine.

[20]  C. Hambly,et al.  Faecal corticosterone concentrations indicate that separately housed male mice are not more stressed than group housed males , 2006, Physiology & Behavior.

[21]  Laura A Conour,et al.  Preparation of animals for research--issues to consider for rodents and rabbits. , 2006, ILAR journal.

[22]  A. Avery,et al.  Environmental enrichment for laboratory rodents. , 2005, ILAR journal.

[23]  Abigail L. Smith,et al.  Modifications to husbandry and housing conditions of laboratory rodents for improved well-being. , 2005, ILAR journal.

[24]  V. Baumans.  Environmental enrichment for laboratory rodents and rabbits: requirements of rodents, rabbits, and research. , 2005, ILAR journal.

[25]  Roger M. Nitsch,et al.  Laboratory animal welfare: Cage enrichment and mouse behaviour , 2004, Nature.

[26]  E. Alleva,et al.  Long-term effects of the periadolescent environment on exploratory activity and aggressive behaviour in mice: social versus physical enrichment , 2004, Physiology & Behavior.

[27]  V. Baumans,et al.  Preference for social contact versus environmental enrichment in male laboratory mice , 2004, Laboratory animals.

[28]  V. Baumans,et al.  Male management: coping with aggression problems in male laboratory mice , 2003, Laboratory animals.

[29]  A. Barnekow,et al.  Effects of different forms of environmental enrichment on behavioral, endocrinological, and immunological parameters in male mice , 2003, Hormones and Behavior.

[30]  P. Tsai,et al.  Impact of environmental enrichment in mice. 1: Effect of housing conditions on body weight, organ weights and haematology in different strains , 2002, Laboratory animals.

[31]  I. Olsson,et al.  Improving housing conditions for laboratory mice: a review of 'environmental enrichment' , 2002, Laboratory animals.

[32]  L. V. Zutphen,et al.  Influence of cage enrichment on aggressive behaviour and physiological parameters in male mice , 2002 .

[33]  K. Miczek,et al.  Aggressive behavioral phenotypes in mice , 2001, Behavioural Brain Research.

[34]  Vera Baumans,et al.  Modulation of aggression in male mice: influence of group size and cage size , 2001, Physiology & Behavior.

[35]  H. Würbel.  Ideal homes? Housing effects on rodent brain and behaviour , 2001, Trends in Neurosciences.

[36]  D. Morton,et al.  The Use of Cage Enrichment to Reduce Male Mouse Aggression , 2000 .

[37]  C. Barnard,et al.  Strain-Specific Effects of Cage Enrichment in Male Laboratory Mice (Mus Musculus) , 1999, Animal Welfare.

[38]  J. Caston,et al.  Rearing Environmental Enrichment in Two Inbred Strains of Mice: 1. Effects on Emotional Reactivity , 1999, Behavior genetics.

[39]  J. Hurst,et al.  Competitive behaviour in an island population of house mice,Mus domesticus , 1998, Animal Behaviour.

[40]  K. Armstrong,et al.  Use of Corn-Husk Nesting Material to Reduce Aggression in Caged Mice. , 1998, Contemporary topics in laboratory animal science.

[41]  P. Brain,et al.  Refining rodent husbandry: the mouse: Report of the Rodent Refinement Working Party , 1998, Laboratory animals.

[42]  H. D. Weerd.  Evaluation of environmental enrichment for laboratory mice. , 1997 .

[43]  C. Nicol,et al.  Behavioural demand functions of caged laboratory mice for additional space , 1997, Animal Behaviour.

[44]  A. Haemisch,et al.  Effects of cage enrichment on territorial aggression and stress physiology in male laboratory mice. , 1997, Acta physiologica Scandinavica. Supplementum.

[45]  H. van de Weerd.  Evaluation of environmental enrichment for laboratory mice. , 1997, The Veterinary quarterly.

[46]  C. Barnard,et al.  Environmental Enrichment, Immunocompetence, and Resistance to Babesia microti in Male Mice , 1996, Physiology & Behavior.

[47]  J. Koolhaas,et al.  A comparison between house mouse lines selected for attack latency or nest-building: Evidence for a genetic basis of alternative behavioral strategies , 1995, Behavior genetics.

[48]  K. Militzer,et al.  Environmental enrichment and aggressive behaviour: Influence on body weight and body fat in male inbred HLG mice , 1995 .

[49]  T. Voss,et al.  Effects of environmental enrichment on aggressive behavior, dominance hierarchies, and endocrine states in male DBA/2J mice , 1994, Physiology & Behavior.

[50]  A. Haemisch,et al.  The cage design affects intermale aggression in small groups of male laboratory mice: strain specific consequences on social organization, and endocrine activations in two inbred strains (DBA/2J and CBA/J). , 1994, Journal of experimental animal science.

[51]  D. S. Watson.  Evaluation of inanimate objects on commonly monitored variables in preclinical safety studies for mice and rats. , 1993, Laboratory animal science.

[52]  C. Barnard,et al.  The role of substrate odours in maintaining social tolerance between male house mice, Mus musculus domesticus , 1993, Animal Behaviour.

[53]  P. McGregor,et al.  Varied Cages Result in More Aggression in Male CFLP Mice , 1990 .

[54]  B. Ohlsson-Wilhelm,et al.  Effect of cage population density on plasma corticosterone and peripheral lymphocyte populations of laboratory mice , 1989, Laboratory animals.

[55]  A. Chamove.  Cage design reduces emotionality in mice , 1989, Laboratory animals.

[56]  G. Schnell,et al.  Influence of environmental complexity and space on social interactions of mice (Mus musculus and Peromyscus leucopus) , 1986 .

[57]  R. G. Butler.  Population size, social behaviour, and dispersal in house mice: A quantitative investigation , 1980, Animal Behaviour.

[58]  N. Henderson,et al.  Short exposures to enriched environments can increase genetic variability of behavior in mice. , 1976, Developmental psychobiology.

[59]  P. Brain.  What does individual housing mean to a mouse? , 1975, Life sciences.

[60]  J. H. Mackintosh.  Factors affecting the recognition of territory boundaries by mice (Mus musculus) , 1973 .

[61]  J. P. Hegmann,et al.  Genetic differences influencing behavioral temperature regulation in small mammals. I. Nesting byMus musculus , 1972, Behavior genetics.

[62]  J. H. Mackintosh.  Territory formation by laboratory mice , 1970 .

[63]  S. Friedman,et al.  Hormonal stimulation necessary for elicitation of maternal nest-building in the mouse (Mus musculus). , 1969, Animal behaviour.

[64]  G. Dunnet,et al.  Mice All Over. , 1967 .

[65]  J. P. Scott,et al.  The Causes of Fighting in Mice and Rats , 1951, Physiological Zoology.