Home cage activity and behavioral performance in inbred and hybrid mice

Locomotor activity is a key component in many behavioral tests, suggesting that genetic differences in activity levels may be a critical consideration when comparing mouse strains. In order to assess the relationship between activity and performance, we recorded home cage activity, and locomotion and defecation, a non-activity-linked behavior, in tests of anxiety in inbred (C57BL/6J (B6), n = 25; BALB/cJ (C), n = 24; DBA/2J (D2), n = 28) and hybrid (CB6F1/6J (CB6: B6 x C) n = 19) mice. Under our test conditions, the strains showed significant differences in home cage activity levels: C > B6 > D2. The CB6 mice were similar to the B6 mice in horizontal activity and were intermediate between the parental strains in vertical movement. Based on measures of locomotion and defecation in the open field, emergence and novel object tests, and the elevated zero maze, the C mice appeared to be the most anxious and the B6 were the least anxious. The D2 mice were intermediate on some measures but more similar to B6 mice on others, making ranking them more difficult. In addition, the CB6 mice displayed characteristics of both parental strains. They had greater similarity to B6 mice in measures of horizontal movement in the home cage and locomotion in the open field and emergence tests, but exhibited defecation responses similar to those of C mice in the novel object test and elevated zero maze. The results suggest that strain differences in spontaneous locomotion should be considered when interpreting strain differences in behavioral tests, and that home cage activity may be a useful interpretive aid.

[1]  L. G. Davis,et al.  Baseline exploratory activity predicts anxiolytic responsiveness to diazepam in five mouse strains , 1982, Brain Research Bulletin.

[2]  A. C. Collins,et al.  Genetic influences on nicotine responses , 1989, Pharmacology Biochemistry and Behavior.

[3]  L. B. Brown,et al.  Visual stimulus complexity and approach behavior in rats , 1971 .

[4]  C. Belzung Hippocampal mossy fibres: implication in novelty reactions or in anxiety behaviours? , 1992, Behavioural Brain Research.

[5]  S. Paul,et al.  Characterization of benzodiazepine-sensitive behaviors in the A/J and C57BL/6J inbred strains of mice , 1994, Behavior genetics.

[6]  M. W. Weir,et al.  Open-Field Behavior in Mice: Evidence for a Major Gene Effect Mediated by the Visual System , 1966, Science.

[7]  T. Steckler,et al.  Behavioural analysis of four mouse strains in an anxiety test battery , 2000, Behavioural Brain Research.

[8]  C. S. Hall,et al.  Emotional behavior in the rat. III. The relationship between emotionality and ambulatory activity. , 1936 .

[9]  W. N. Dember,et al.  Response by the rat to environmental change. , 1956, Journal of comparative and physiological psychology.

[10]  N. Henderson,et al.  A genetic analysis of spontaneous alternation in mice , 1970, Behavior genetics.

[11]  Orfeu M Buxton,et al.  Locomotor response to an open field during C57BL/6J active and inactive phases differences dependent on conditions of illumination , 2000, Physiology & Behavior.

[12]  T. Lipina,et al.  Features of the Genetically Defined Anxiety in Mice , 2000, Behavior genetics.

[13]  J. Crabbe Genetic differences in locomotor activation in mice , 1986, Pharmacology Biochemistry and Behavior.

[14]  Antonio Caprioli,et al.  Spatial learning and memory, maze running strategies and cholinergic mechanisms in two inbred strains of mice , 1985, Behavioural Brain Research.

[15]  R. Rodgers,et al.  Factor analysis of spatiotemporal and ethological measures in the murine elevated plus-maze test of anxiety , 1995, Pharmacology Biochemistry and Behavior.

[16]  R. Rodgers Animal models of 'anxiety': where next? , 1997, Behavioural pharmacology.

[17]  M. J. Renner,et al.  Scopolamine suppresses both locomotion and object contact in a free-exploration situation , 1992, Pharmacology Biochemistry and Behavior.

[18]  A. C. Collins,et al.  A simple genetic basis for a complex psychological trait in laboratory mice , 1995, Science.

[19]  R. Rodgers,et al.  Effects of benzodiazepine receptor antagonist, flumazenil, on antinociceptive and behavioural responses to the elevated plus-maze in mice , 1991, Neuropharmacology.

[20]  Allan Collins,et al.  Behavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies , 1997, Psychopharmacology.

[21]  J. Vernikos,et al.  Plasma corticosterone concentrations sensitively reflect levels of stimulus intensity in the rat , 1979, Physiology & Behavior.

[22]  Jonathan Flint,et al.  QTL analysis identifies multiple behavioral dimensions in ethological tests of anxiety in laboratory mice , 2001, Current Biology.

[23]  J. Witte,et al.  Genetic dissection of complex traits. , 1994, Nature genetics.

[24]  M. Low,et al.  Dopamine D4 Receptor-Knock-Out Mice Exhibit Reduced Exploration of Novel Stimuli , 1999, The Journal of Neuroscience.

[25]  W. I. Welker,et al.  “Free” versus “Forced” Exploration of a Novel Situation by Rats , 1957 .

[26]  E. Garcia-Rill,et al.  Arousal and locomotion: from schizophrenia to narcolepsy. , 1996, Progress in brain research.

[27]  Frank W. Finger,et al.  Measuring Behavioral Activity , 1972 .

[28]  D. Lawson,et al.  The effects of routine cage-changing on cardiovascular and behavioral parameters in male Sprague-Dawley rats. , 2001, Contemporary topics in laboratory animal science.

[29]  J. Defries,et al.  Response to 30 generations of selection for open-field activity in laboratory mice , 1978, Behavior genetics.

[30]  M. Decker,et al.  The Behavioral Assessment of Sensorimotor Processes in the Mouse: Acoustic Startle, Locomotor Activity, RotaRod, and Beam Walking , 2000 .

[31]  S. Paul,et al.  Towards a genetics of anxious temperament: from mice to men , 1998, Acta psychiatrica Scandinavica. Supplementum.

[32]  Marc Cigrang,et al.  Does neophobia necessarily imply fear or anxiety? , 1986, Behavioural Processes.

[33]  K. Montgomery,et al.  The relation between fear induced by novel stimulation and exploratory drive. , 1955 .

[34]  R. Porsolt,et al.  Habituation of exploratory activity in mice: A screening test for memory enhancing drugs , 2004, Psychopharmacology.

[35]  N. Henderson,et al.  Predicting relationships between psychological constructs and genetic characters: An analysis of changing genetic influences on activity in mice , 1986, Behavior genetics.

[36]  J. Buccafusco Methods of Behavior Analysis in Neuroscience , 2000 .

[37]  C. S. Hall,et al.  Emotional behavior in the rat. I. Defecation and urination as measures of individual differences in emotionality. , 1934 .

[38]  G. Griebel,et al.  Measuring normal and pathological anxiety-like behaviour in mice: a review , 2001, Behavioural Brain Research.