The elevated plus-maze test: Differential psychopharmacology of anxiety-related behavior

Emotion Review

Volumn 4, Issue 1, 2012, Pages 98-115

  Pawlak, Cornelius R ^a,b,c   Karrenbauer, Britta D ^d   Schneider, Peggy ^e   Ho, Ying Jui ^f  

^a CENTRAL INSTITUTE OF MENTAL HEALTH   (Germany)

^b UNIVERSITY OF MANNHEIM   (Germany)

^c GOETHE UNIVERSITY   (Germany)

^d PHILIPPS UNIVERSITY MARBURG   (Germany)

^e Central Institute of Mental Health   (Germany)

^f CHUNG SHAN MEDICAL UNIVERSITY   (Taiwan)

Author keywords

anxiety; avoidance behavior; basal ganglia; differential psychopharmacology; emotion; exploration behavior; fear; high open arm (HOA); individuality; low open arm (LOA); motivation; one trial tolerance; personality; striatum; traits; translational

Indexed keywords

EID: 84856487873     PISSN: 17540739     EISSN: None     Source Type: Journal    
DOI: 10.1177/1754073911421374     Document Type: Review

References (180)

1. Abramson L. Y., Seligman M. E. P. Psychopathology: Experimental models. Maser J. D. Seligman M. E. P., ed. San Francisco, CA: Freeman ; 1977: 1-26.
2. Almeida S. S., Garcia R. A., de Oliveira L. M.. Effects of early protein malnutrition and repeated testing upon locomotor and exploratory behaviors in the elevated plus-maze. Physiology & Behavior. 1993 ; 54: 749-752
3. Almeida S. S., Tonkiss J., Galler J. R.. Prenatal protein malnutrition affects exploratory behavior of female rats in the elevated plus-maze test. Physiology & Behavior. 1996 ; 60: 675-680
4. Amelang M., Bartussek D., Stemmler G., Hagemann D. Differentielle Psychologie und Persönlichkeitsforschung. 2006 ). Differentielle Psychologie und Persönlichkeitsforschung [Differential psychology and personality research] (6th ed.). Stuttgart, Germany: Kohlhammer. Stuttgart, Germany: Kohlhammer ; 2006 :
5. Andrade M. M. M., Tomé M. F., Santiago E. S., Lúcia-Santos A., de Andrade T. G. C. S.. Longitudinal study of daily variation of rats' behavior in the elevated plus-maze. Physiology & Behavior. 2003 ; 78: 125-133
6. Andreatini R., Blanchard C., Blanchard R., Brandão M. L., Carobrez A. P., Griebel G.,... Graeff F. G.. The brain decade in debate: II. Panic or anxiety? From animal models to a neurobiological basis. Brazilian Journal of Medical and Biological Research. 2001 ; 34: 145-154
7. Andreatini R., Vital M. A. B. F., Santos G. L.. The reinstatement of conflict reverses the one-trial tolerance to diazepam on elevated plus-maze. European Neuropsychopharmacology. 2003 ; 13 (Suppl. 4). 378-379
8. Andrews N., File S. E.. Handling history of rats modifies behavioural effects of drugs in the elevated plus-maze test of anxiety. European Journal of Pharmacology. 1993 ; 235: 109-112
9. Barlow D. H. Anxiety and its disorders: The nature and treatment of anxiety and panic. 2002 ). Anxiety and its disorders: The nature and treatment of anxiety and panic (2nd ed.). New York, NY: Guilford Press. New York, NY: Guilford Press ; 2002 :
10. Bauhofer A., Schwarting R. K. W., Köster M., Schmitt A., Lorenz W., Pawlak C. R.. Sickness behavior of rats with abdominal sepsis can be improved by antibiotic and G-CSF prophylaxis in clinic modeling randomized trials. Inflammation Research. 2004 ; 53: 697-705
11. Binder E., Droste S. K., Ohl F., Reul J. M. H. M.. Regular voluntary exercise reduces anxiety-related behaviour and impulsiveness in mice. Behavioural Brain Research. 2004 ; 155: 197-206
12. Blanchard D. C., Blanchard R. J.. Ethoexperimental approaches to the biology of emotion. Annual Review of Psychology. 1988 ; 39: 43-68
13. Blanchard R. J., Blanchard D. C.. Antipredator defensive behaviors in a visible burrow system. Journal of Comparative Psychology. 1989 ; 103: 70-82
14. Blanchard R. J., Blanchard D. C. Anxiety. McNaughton N. Andrews G., ed. Dunedin, New Zealand: Otago University Press ; 1990: 124-133.
15. Blanchard R. J., Parmigiani S., Bjornson C., Masuda C., Weiss S. M., Blanchard D. C.. Antipredator behaviour of Swiss-Webster mice in a visible burrow system. Aggressive Behavior. 1995 ; 21: 123-136
16. Blanchard R. J., Yudko E. B., Rodgers R. J., Blanchard D. C.. Defense system psychopharmacology: An ethological approach to the pharmacology of fear and anxiety. Behavioural Brain Research. 1993 ; 58: 155-165
17. Modern Trends in Pharmacopsychiatry. Boissier J. R., ed. Karger: Basel ; 1978: 143-156.
18. Borsini F., Podhorna J., Marazziti D.. Do animal models of anxiety predict anxiolytic-like effects of antidepressants?. Psychopharmacology. 2002 ; 163: 121-141
19. Borta A., Schwarting R. K. W.. Inhibitory avoidance, pain reactivity, and plus-maze behaviour in Wistar rats with high versus low rearing activity. Physiology & Behavior. 2005a ; 84: 387-396
20. Borta A., Schwarting R. K. W.. Post-trial treatment with the nicotinic agonist metanicotine: Differential effects in Wistar rats with high versus low rearing activity. Pharmacology, Biochemistry and Behavior. 2005b ; 80: 541-548
21. Borta A., Wöhr M., Schwarting R. K. W.. Rat ultrasonic vocalization in aversively motivated situations and the role of individual differences in anxiety-related behavior. Behavioural Brain Research. 2006 ; 166: 271-280
22. Bouchard T. J.. Genes, environment, and personality. Science. 1994 ; 264: 1700-1701
23. Brioni J. D., Orsingher O. A.. Operant behavior and reactivity to the anticonflict effect of diazepam in perinatally undernourished rats. Physiology & Behavior. 1988 ; 44: 193-198
24. Bucán M., Abel T.. The mouse: Genetics meets behaviour. Nature Reviews Genetics. 2002 ; 3: 114-123
25. Calder A. J., Lawrence A. D., Young A. W.. Neuropsychology of fear and loathing. Nature Reviews Neuroscience. 2001 ; 2: 352-363
26. Canto-de-Souza A., Nunes-de-Souza R. L., Rodgers R. J.. Anxiolytic-like effect of way-100635 microinfusions into the median (but not dorsal) raphe nucleus in mice exposed to the plus-maze: Influence of prior test experience. Brain Research. 2002 ; 928: 50-59
27. Capitanio J. P.. Early experience and social processes in rhesus macaques (Macaca mulatta): II. Complex social interaction. Journal of Comparative Psychology. 1985 ; 99: 133-144
28. Carobrez A. P., Bertoglio L. J.. Ethological and temporal analyses of anxiety-like behavior: The elevated plus-maze model 20 years on. Neuroscience & Biobehavioral Reviews. 2005 ; 29: 1193-1205
29. Carver C. S.. Impulse and constraint: Perspectives from personality psychology, convergence with theory in other areas, and potential for integration. Personality and Social Psychology Review. 2005 ; 9: 312-333
30. Clément Y., Calatayud F., Belzung C.. Genetic basis of anxiety-like behaviour: A critical review. Brain Research Bulletin. 2002 ; 57: 57-71
31. Cloninger C. R., Svrakic D. M., Przybeck T. R.. A psychobiological model of temperament and character. Archives of General Psychiatry. 1993 ; 50: 975-990
32. Crabbe J. C., Wahlsten D., Dudek B. C.. Genetics of mouse behavior: Interactions with laboratory environment. Science. 1999 ; 284: 1670-1672
33. Cruz-Morales S. E., Santos N. R., Brandão M. L.. One-trial tolerance to midazolam is due to enhancement of fear and reduction of anxiolytic-sensitive behaviors in the elevated plus-maze retest in the rat. Pharmacology, Biochemistry and Behavior. 2002 ; 72: 973-978
34. Dantzer R., O'Connor J. C., Freund G. G., Johnson R. W., Kelley K. W.. From inflammation to sickness and depression: When the immune system subjugates the brain. Nature Reviews Neuroscience. 2008 ; 9: 46-57
35. Davis M., Walker D., Lee Y.. Roles of the amygdala and bed nucleus of the stria terminalis in fear and anxiety measured with the acoustic startle reflex. Possible relevance to PTSD. Annals of the New York Academy of Sciences. 1997 ; 821: 305-331
36. Deakin J. F. W., Graeff F. G.. 5-HT and mechanisms of defence. Journal of Psychopharmacology. 1991 ; 5: 305-315
37. Depue R., Lenzenweger M. Theories of personality disorders. 2005 ). A neurobehavioral dimensional model of personality disturbance. In LenzenwegerM.ClarkinJ. (Eds.), Theories of personality disorders (2nd ed.) (pp. 136-176). New York, NY: Guilford Press. Lenzenweger M. Clarkin J., ed. New York, NY: Guilford Press ; 2005: 136-176.
38. Dere E., De Souza-Silva M. A., Frisch C., Teubner B., Söhl G., Willecke K., Huston J. P.. Connexin30-deficient mice show increased emotionality and decreased rearing activity in the open-field along with neurochemical changes. European Journal of Neuroscience. 2003 ; 18: 629-638
39. Enkel T., Gholizadeh D., von Bohlen und Halbach O., Sanchis-Segura C., Hurlemann R., Spanagel R.,... Vollmayr B.. Ambiguous-cue interpretation is biased under stress- and depression-like states in rats. Neuropsychopharmacology. 2010 ; 35: 1008-1015
40. Fedotova J. O., Hartmann G., Lénárd L., Sapronov N. S.. Effects of 5-HT1A receptor agonist and antagonist on anxiety in intact and ovariectomized female rats. Acta Physiologica Hungarica. 2004 ; 91: 175-184
41. Fernandes C., File S. E.. The influence of open arm ledges and maze experience in the elevated plus-maze. Pharmacology, Biochemistry and Behavior. 1996 ; 54: 31-40
42. Fernández-Teruel A., Escorihuela R. M., Gray J. A., Aguilar R., Gil L., Giménez-Llort L.,... Flint J.. A quantitative trait locus influencing anxiety in the laboratory rat. Genome Research. 2002 ; 12: 618-626
43. Ferreira T. L., Moreira K. M., Ikeda D. C., Bueno O. F. A., Oliveira M. G. M.. Effects of dorsal striatum lesions in tone fear conditioning and contextual fear conditioning. Brain Research. 2003 ; 987: 17-24
44. File S. E.. One-trial tolerance to the anxiolytic effects of chlordiazepoxide in the plus-maze. Psychopharmacology. 1990 ; 100: 281-282
45. File S. E.. Factors controlling measures of anxiety and responses to novelty in the mouse. Behavioural Brain Research. 2001 ; 125: 151-157
46. File S. E., Andrews N., Wu P. Y., Zharkovsky A., Zangrossi H.. Modification of chlordiazepoxide's behavioural and neurochemical effects by handling and plus-maze experience. European Journal of Pharmacology. 1992 ; 218: 9-14
47. File S. E., Gonzalez L. E., Gallant R.. Role of the basolateral nucleus of the amygdala in the formation of a phobia. Neuropsychopharmacology. 1998 ; 19: 397-405
48. File S. E., Kenny P. J., Cheeta S.. The role of the dorsal hippocampal serotonergic and cholinergic systems in the modulation of anxiety. Pharmacology Biochemistry and Behavior. 2000 ; 66: 65-72
49. File S. E., Mabbutt P. S., Hitchcott P.. Characterisation of the phenomenon of "one-trial tolerance" to the anxiolytic effect of chlordiazepoxide in the elevated plus-maze. Psychopharmacology. 1990 ; 102: 98-101
50. File S. E., Zangrossi H.. "One-trial tolerance" to the anxiolytic actions of benzodiazepines in the elevated plus-maze, or the development of a phobic state?. Psychopharmacology. 1993 ; 110: 240-244
51. File S. E., Zangrossi H., Viana M., Graeff F. G.. Trial 2 in the elevated plus-maze: A different form of fear?. Psychopharmacology. 1993 ; 111: 491-494
52. Finn D. A., Rutledge-Gorman M. T., Crabbe J. C.. Genetic animal models of anxiety. Neurogenetics. 2003 ; 4: 109-135
53. Flint J.. Analysis of quantitative trait loci that influence animal behavior. Journal of Neurobiology. 2003 ; 54: 46-77
54. Francis R. C.. Temperament in a fish: A longitudinal study of the development of individual differences in aggression and social rank in the Midas cichlid. Ethology. 1990 ; 86: 311-325
55. Frussa-Filho R., de Ribeiro R. A.. One-trial tolerance to the effects of chlordiazepoxide in the elevated plus-maze is not due to acquisition of a phobic avoidance of open arms during initial exposure. Life Sciences. 2002 ; 71: 519-525
56. Garbe C. M., Kemble E. D.. Effects of prior agonistic experience on risk assessment and approach behavior evoked by familiar and unfamiliar conspecific odors. Aggressive Behavior. 1994 ; 20: 143-149
57. Garcia A. M. B., Cardenas F. P., Morato S.. Effect of different illumination levels on rat behavior in the elevated plus-maze. Physiology & Behavior. 2005 ; 85: 265-270
58. Gonzalez L. E., File S. E.. A five minute experience in the elevated plus-maze alters the state of benzodiazepine receptor in the dorsal raphe nucleus. The Journal of Neuroscience. 1997 ; 17: 1505-1511
59. Gosling S. D.. Personality dimensions in spotted hyenas (Crocuta crocuta. Journal of Comparative Psychology. 1998 ; 112: 107-118
60. Gosling S. D.. From mice to men: What can we learn about personality from animal research?. Psychological Bulletin. 2001 ; 127: 45-86
61. Graeff F. G.. Neuroanatomy and neurotransmitter regulation of defensive behaviors and related emotions in animals. Brazilian Journal of Medical and Biological Research. 1994 ; 27: 811-829
62. Graeff F. G., Guimarães F. S., De Andrade T. G. C. S., Deakin J. F. W.. Role of 5-HT in stress, anxiety, and depression. Pharmacology, Biochemistry and Behavior. 1996 ; 54: 129-141
63. Gray J. A. The neuropsychology of anxiety: An enquiry into the functions of the septo-hippocampal system. 1982 ). The neuropsychology of anxiety: An enquiry into the functions of the septo-hippocampal system (1st ed.). Oxford, UK: Oxford University Press. Oxford, UK: Oxford University Press ; 1982 :
64. Gray J. A., McNaughton N. The neuropsychology of anxiety: An enquiry into the functions of the septo-hippocampal system. 2000 ). The neuropsychology of anxiety: An enquiry into the functions of the septo-hippocampal system (2nd ed.). Oxford, UK: Oxford University Press. Oxford, UK: Oxford University Press ; 2000 :
65. Graybiel A. M., Rauch S. L.. Toward a neurobiology of obsessive-compulsive disorder. Neuron. 2000 ; 28: 343-347
66. Gross C., Hen R.. The developmental origins of anxiety. Nature Reviews Neuroscience. 2004 ; 5: 545-552
67. Halliday T. R.. The libidinous newt: An analysis of variations in the sexual behaviour of the male smooth newt. Triturus vulgaris. Animal Behaviour. 1976 ; 24: 398-414
68. Handley S. L., McBlane J. W.. 5-HT drugs in animal models of anxiety. Psychopharmacology. 1993 ; 112: 13-20
69. Hasler G., Fromm S., Alvarez R. P., Luckenbaugh D. A., Drevets W. C., Grillon C.. Cerebral blood flow in immediate and sustained anxiety. The Journal of Neuroscience. 2007 ; 27: 6313-6319
70. Hasuo C.. Effects of milieu upon character: I. Experiments with young chickens. Japanese Journal of Experimental Psychology. 1935 ; 2: 109-118
71. Hebb D. O.. Temperament in chimpanzees: I. Method and analyses. The Journal of Comparative and Physiological Psychology. 1949 ; 42: 192-206
72. Henn F. A., Vollmayr B.. Stress models of depression: Forming genetically vulnerable strains. Neuroscience & Biobehavioral Reviews. 2005 ; 29: 799-804
73. Ho Y. J., Eichendorff J., Schwarting R. K. W.. Individual response profiles of male Wistar rats in animal models for anxiety and depression. Behavioural Brain Research. 2002 ; 136: 1-12
74. Ho Y. J., Pawlak C. R., Guo L., Schwarting R. K. W.. Acute and long-term consequences of single MDMA administration in relation to individual anxiety levels in the rat. Behavioural Brain Research. 2004 ; 149: 135-144
75. Ho Y. J., Wang C. F., Hsu W. Y., Tseng T., Hsu C. C., Kao M. D., Tsai Y. F.. Psychoimmunological effects of dioscorea in ovariectomized rats: Role of anxiety level. Annals of General Psychiatry. 2007 ; 6: 21
76. Hogg S.. A review of the validity and variability of the elevated plus-maze as an animal model of anxiety. Pharmacology, Biochemistry and Behavior. 1996 ; 54: 21-30
77. Holmes A., Rodgers R. J.. Responses of Swiss-Webster mice to repeated plus-maze experience: Further evidence for a qualitative shift in emotional state?. Pharmacology, Biochemistry and Behavior. 1998 ; 60: 473-488
78. Horvitz J. C.. Mesolimbocortical and nigrostriatal dopamine responses to salient non-reward events. Neuroscience. 2000 ; 96: 651-656
79. Jensen J., McIntosh A. R., Crawley A. P., Mikulis D. J., Remington G., Kapur S.. Direct activation of the ventral striatum in anticipation of aversive stimuli. Neuron. 2003 ; 40: 1251-1257
80. Kabbaj M., Akil H.. Individual differences in novelty-seeking behavior in rats: A c-fos study. Neuroscience. 2001 ; 106: 535-545
81. Kaesermann H. P.. Stretched attend posture, a non-social form of ambivalence, is sensitive to a conflict-reducing drug action. Psychopharmacology. 1986 ; 89: 31-37
82. Karl T., Pabst R., von Hörsten S.. Behavioral phenotyping of mice in pharmacological and toxicological research. Experimental and Toxicologic Pathology. 2003 ; 55: 69-83
83. Karrenbauer B. D., Ho Y. J., Ludwig V., Löhn J., Spanagel R., Schwarting R. K. W., Pawlak C. R.. Time-dependent effects of striatal interleukin-2 on open field behaviour in rats. Journal of Neuroimmunology. 2009 ; 208: 10-18
84. Khan A. A., Jacobson K. C., Gardner C. O., Prescott C. A., Kendler K. S.. Personality and comorbidity of common psychiatric disorders. British Journal of Psychiatry. 2005 ; 186: 190-196
85. Kitabatake Y., Hikida T., Watanabe D., Pastan I., Nakanishi S.. Impairment of reward-related learning by cholinergic cell ablation in the striatum. Proceedings of the National Academy of Sciences, USA. 2003 ; 100: 7965-7970
86. Kõks S., Beljajev S., Koovit I., Abramov U., Bourin M., Vasar E.. 8-OH-DPAT, but not deramciclane, antagonizes the anxiogenic-like action of paroxetine in an elevated plus-maze. Psychopharmacology. 2001 ; 153: 365-372
87. Laakso A., Wallius E., Kajander J., Bergman J., Eskola O., Solin O.,... Hietala J.. Personality traits and striatal dopamine synthesis capacity in healthy subjects. American Journal of Psychiatry. 2003 ; 160: 904-910
88. Lathe R.. The individuality of mice. Genes, Brain and Behavior. 2004 ; 3: 317-327
89. LeDoux J. E.. Emotion circuits in the brain. Annual Review of Neuroscience. 2000 ; 23: 155-184
90. Letwin N. E., Kafkafi N., Benjamini Y., Mayo C., Frank B. C., Luu T.,... Elmer G. I.. Combined application of behavior genetics and microarray analysis to identify regional expression themes and gene-behaviour associations. The Journal of Neuroscience. 2006 ; 26: 5277-5287
91. Liebsch G., Wotjak C. T., Landgraf R., Engelmann M.. Septal vasopressin modulates anxiety-related behaviour in rats. Neuroscience Letters. 1996 ; 217: 101-104
92. Lister R. G.. The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology. 1987 ; 92: 180-185
93. London E. D., Simon S. L., Berman S. M., Mandelkern M. A., Lichtman A. M., Bramen J.,... Ling W.. Mood disturbances and regional cerebral metabolic abnormalities in recently abstinent methamphetamine abusers. Archives of General Psychiatry. 2004 ; 61: 73-84
94. Lorberbaum J. P., Kose S., Johnson M. R., Arana G. W., Sullivan L. K., Hamner M. B.,... George M. S.. Neural correlates of speech anticipatory anxiety in generalized social phobia. Neuroreport. 2004 ; 15: 2701-2705
95. Ludwig V., Mihov Y., Schwarting R. K. W.. Behavioral and neurochemical consequences of multiple MDMA administrations in the rat: Role of individual differences in anxiety-related behavior. Behavioural Brain Research. 2008 ; 189: 52-64
96. Lui S., Huang X., Chen L., Tang H., Zhang T., Li X.,... Gong Q.. High-field MRI reveals an acute impact on brain function in survivors of the magnitude 8.0 earthquake in China. Proceedings of the National Academy of Sciences of the United States of America. 2009 ; 106: 15412-15417
97. Marks I. M. Fears, phobias, and rituals: Panic, anxiety, and their disorders. New York, NY: Oxford University Press ; 1987 :
98. Marks I. M., Nesse R. M.. Fear and fitness: An evolutionary analysis of anxiety disorders. Ethology and Sociobiology. 1994 ; 15: 147-161
99. Mathew S. J., Ho S.. Etiology and neurobiology of social anxiety disorder. Journal of Clinical Psychiatry. 2006 ; 67 (Suppl. 12). 9-13
100. McKinney W. T., Bunney W. E.. Animal models of depression: I. Review of evidence: Implications for research. Archives of General Psychiatry. 1969 ; 21: 240-248
101. McNaughton N., Corr P. J.. A two-dimensional neuropsychology of defense: Fear/anxiety and defensive distance. Neuroscience & Biobehavioral Reviews. 2004 ; 28: 285-305
102. Mehta P. H., Gosling S. D.. Bridging human and animal research: A comparative approach to studies of personality and health. Brain, Behavior, and Immunity. 2008 ; 22: 651-661
103. Millan M. J.. The neurobiology and control of anxious states. Progress in Neurobiology. 2003 ; 70: 83-244
104. Molewijk H. E., van der Poel A. M., Olivier B.. The ambivalent behaviour "stretched approach posture" as a paradigm to characterize anxiolytic drugs. Psychopharmacology. 1995 ; 121: 81-90
105. Montgomery K. C.. The relation between fear induced by novel stimulation and exploratory behaviour. The Journal of Comparative and Physiological Psychology. 1955 ; 48: 254-260
106. Morris P. H., Gale A., Duffy K.. Can judges agree on the personality of horses?. Personality and Individual Differences. 2002 ; 33: 67-81
107. Motta V., Maisonnette S., Morato S., Castrechini P., Brandão M. L.. Effects of blockade of 5-HT2 receptors and activation of 5-HT1A receptors on the exploratory activity of rats in the elevated plus-maze. Psychopharmacology. 1992 ; 107: 135-139
108. Noblett K. L., Coccaro E. F.. Molecular genetics of personality. Current Psychiatry Reports. 2005 ; 7: 73-80
109. Nunes-de-Souza R. L., Canto-de-Souza A., Rodgers R. J.. Effects of intra-hippocampal infusion of WAY-100635 on plus-maze behavior in mice. Influence of site of injection and prior test experience. Brain Research. 2002 ; 927: 87-96
110. Ohl F.. Testing for anxiety. Clinical Neuroscience Research. 2003 ; 3: 233-238
111. Panksepp J. Affective neuroscience: The foundations of human and animal emotions. New York, NY: Oxford University Press ; 1998 :
112. Pawlak C. R., Ho Y. J., Schwarting R. K. W.. Animal models of human psychopathology based on individual differences in novelty-seeking and anxiety. Neuroscience & Biobehavioral Reviews. 2008 ; 32: 1544-1568
113. Pawlak C. R., Ho Y. J., Schwarting R. K. W., Bauhofer A.. Relationship between striatal levels of interleukin-2 mRNA and plus-maze behaviour in the rat. Neuroscience Letters. 2003 ; 341: 205-208
114. Pawlak C. R., Schwarting R. K. W.. Object preference and nicotine consumption in rats with high vs. low rearing activity in a novel open field. Pharmacology, Biochemistry and Behavior. 2002 ; 73: 679-687
115. Pawlak C. R., Schwarting R. K. W.. Striatal microinjections of interleukin-2 and rat behaviour in the elevated plus-maze. Behavioural Brain Research. 2006a ; 168: 339-344
116. PawlakC. R.SchwartingR. K. W. (2006b). Interleukin-2 in the striatum affects motivated open field behaviour in rats. Program No. A078.7. 2006 Abstract Viewer/Itinerary Planner. Abstract retrieved from http://www. abstractsonline.com/viewer/viewAbstractPrintFriendly.asp?CKey= %7bDED5B473-0476-446A-8ECB-C77B2E89DAA6%7d&SKey=%7b9F46C125-548B-4C4F-9017- B8897EEB622E%7d&MKey=%7bD1974E76-28AF-4C1C-8AE8-4F73B56247A7%7d&AKey= %7b3A7DC0B9-D787-44AA-BD08-FA7BB2FE9004%7d
117. Pawlak C. R., Schwarting R. K. W., Bauhofer A.. Cytokine mRNA levels in brain and peripheral tissues of the rat: Relationships with plus-maze behavior. Molecular Brain Research. 2005 ; 137: 159-165
118. Pawlak C. R., Weyers P.. Tiermodelle für Angst und Angststörungen. Ausgewählte Modelle und Ansätze zur Untersuchung individueller Differenzen. Psychologische Rundschau. 2006 ; 57: 139-153
119. Pellow S., Chopin P., File S. E., Briley M.. Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. Journal of Neuroscience Methods. 1985 ; 14: 149-167
120. Pereira J. K. D., Vieira R. J., Konishi C. T., de Ribeiro R. A., Frussa-Filho A.. The phenomenon of "one-trial tolerance" to the anxiolytic effect of chlordiazepoxide in the elevated plus-maze is abolished by the introduction of a motivational conflict situation. Life Sciences. 1999 ; 65: PL101-107
121. Perkins A. M., Ettinger U., Davis R., Foster R., Williams S. C. R., Corr P. J.. Effects of Lorazepam and citalopram on human defensive reactions: Ethopharmacological differentiation of fear and anxiety. The Journal of Neuroscience. 2009 ; 29: 12617-12624
122. Petitto J. M., Lysle D. T., Gariepy J., Lewis M. H.. Association of genetic differences in social behavior and cellular immune responsiveness: Effects of social experience. Brain, Behavior, and Immunity. 1994 ; 8: 111-123
123. Petitto J. M., Lysle D. T., Gariepy J., Clubb P. H., Cairns R. L., Lewis M. H.. Genetic differences in social behavior: Relation to natural killer cell function and susceptibility to tumor development. Neuropsychopharmacology. 1993 ; 8: 35-43
124. Phelps E. A., LeDoux J. E.. Contributions of the amygdala to emotion processing: From animal models to human behavior. Neuron. 2005 ; 48: 175-187
125. Pinel J. P. J., Mana M. J. Ethoexperimental approaches to the study of behavior. Blanchard R. J. Brain P. F. Parmigiani S. Blanchard D. C., ed. Dordrecht, The Netherlands: Kluwer Academic Publishers ; 1989: 137-150.
126. Pinel J. P. J., Treit D.. Burying as a defensive response in rats. The Journal of Comparative and Physiological Psychology. 1978 ; 92: 708-712
127. Raison C. L., Capuron L., Miller A. H.. Cytokines sing the blues: Inflammation and the pathogenesis of depression. Trends in Immunology. 2006 ; 27: 24-31
128. Reiman E. M., Raichle M. E., Robins E., Mintun M. A., Fusselman M. J., Fox P. T.,... Hackman K. A.. Neuroanatomical correlates of a lactate-induced anxiety attack. Archives of General Psychiatry. 1989 ; 46: 493-500
129. Reynolds S. M., Berridge K. C.. Positive and negative motivation in nucleus accumbens shell: Bivalent rostrocaudal gradients for GABA-elicited eating, taste "liking"/"disliking" reactions, place preference/avoidance, and fear. The Journal of Neuroscience. 2002 ; 22: 7308-7320
130. Richard I. H., Schiffer R. B., Kurlan R.. Anxiety and Parkinson's disease. The Journal of Neuropsychiatry and Clinical Neurosciences. 1996 ; 8: 383-392
131. Richelle M.. The integration of behavior as a variable in psychopharmacological research. Journal of Physiology (Paris). 1968 ; 60 (Suppl. 1). 149-203
132. Rodgers R. J.. Animal models of "anxiety": Where next?. Behavioural Pharmacology. 1997 ; 8: 477-496
133. Rodgers R. J., Cao B. J., Dalvi A., Holmes A.. Animal models of anxiety: An ethological perspective. Brazilian Journal of Medical and Biological Research. 1997 ; 30: 289-304
134. Rodgers R. J., Cole J. C.. Influence of social isolation, gender, strain and prior novelty on plus-maze behaviour in mice. Physiology & Behavior. 1993 ; 54: 729-736
135. Rodgers R. J., Lee C., Shepherd J. K.. Effects of diazepam on behavioural and antinociceptive responses to the elevated plus-maze in male mice depend upon treatment regimen and prior maze experience. Psychopharmacology. 1992 ; 106: 102-110
136. Rodgers R. J., Shepherd J. K.. Influence of prior maze experience on behaviour and response to diazepam in the elevated plus-maze and light/dark tests of anxiety in mice. Psychopharmacology. 1993 ; 113: 237-242
137. Rogan M. T., Leon K. S., Perez D. L., Kandel E. R.. Distinct neural signatures for safety and danger in the amygdala and striatum of the mouse. Neuron. 2005 ; 46: 309-320
138. Santucci L. B., Daud M. M., Almeida S. S., de Oliveira L. M.. Effects of early protein malnutrition and environmental stimulation upon the reactivity to diazepam in two animal models of anxiety. Pharmacology, Biochemistry and Behavior. 1994 ; 49: 393-398
139. Sapolsky R. M., Ray J. C.. Styles of dominance and their endocrine correlates among wild olive baboons (Pabio anubis). American Journal of Primatology. 1989 ; 18: 1-13
140. Sareen J., Campbell D. W., Leslie W. D., Malisza K. L., Stein M. B., Paulus M. P.,... Reiss J. P.. Striatal function in generalized social phobia: A functional magnetic resonance imaging study. Biological Psychiatry. 2007 ; 61: 396-404
141. Schenberg E. E., Ferreira T. L., Figueredo L. Z. P., Hipólide D. C., Nobrega J. N., Oliveira M. G. M.. Fear conditioning performance and NMDA receptor subtypes: NR2A differential expression in the striatum. Brain Research Bulletin. 2006 ; 69: 440-446
142. Schiller D., Levy I., Niv Y., Le Doux J. E., Phelps E. A.. From fear to safety and back: Reversal of fear in the human brain. The Journal of Neuroscience. 2008 ; 28: 11517-11525
143. Schneider P., Ho Y.-J., Spanagel R., Pawlak C. R.. A novel elevated plus-maze procedure to avoid the one-trial tolerance problem. Frontiers in Behavioral Neuroscience. 2011 ; 5: 43
144. Schneider P., Spanagel R., Pawlak C. R.. Interleukin-2 affects social interaction behaviour in relation to anxiety-like trait behaviour in the elevated plus-maze in adult Wistar rats. Brain, Behavior, and Immunity. 2009 ; 23 (Suppl. 1). S19
145. SchneiderP.SpanagelR.SchwartingR. K. W.PawlakC. R. (2008). Individual behaviour and relationship between elevated plus-maze and social interaction test in adult rats. Program No. 393. 2008 Abstract Viewer/Itinerary Planner. Poster presented at the Society for Neuroscience 38th Annual Meeting, Washington, DC. Abstract retrieved from http://www.abstractsonline.com/Plan/ ViewAbstract.aspx?sKey=8b033b4b-d7da-4b3a-b196-af4e05aa33bc&cKey= 4dbc1861-fe5c-4be1-874a-1e23ae995d27&mKey=%7bAFEA068D-D012-4520-8E42- 10E4D1AF7944%7d
146. Schoenbaum G., Setlow B.. Lesions of nucleus accumbens disrupt learning about aversive outcomes. The Journal of Neuroscience. 2003 ; 23: 9833-9841
147. Schwabe K., Klein S., Koch M.. Behavioural effects of neonatal lesions of the medial prefrontal cortex and subchronic pubertal treatment with phencyclidine of adult rats. Behavioural Brain Research. 2006 ; 168: 150-160
148. Schwarting R. K. W., Pawlak C. R.. Behavioral neuroscience in the rat: Taking the individual into account. Methods and Findings in Experimental and Clinical Pharmacology. 2004 ; 26 (Suppl. 2). 17-22
149. Schwarting R. K. W., Thiel C. M., Müller C. P., Huston J. P.. Relationship between anxiety and serotonin in the ventral striatum. Neuroreport. 1998 ; 9: 1025-1029
150. Silva R. C. B., Brandão M. L.. Acute and chronic effects of gepirone and fluoxetine in rats tested in the elevated plus-maze: An ethological analysis. Pharmacology, Biochemistry and Behavior. 2000 ; 65: 209-216
151. Smeets W. J. A. J., Marín O., González A.. Evolution of the basal ganglia: New perspectives through a comparative approach. Journal of Anatomy. 2000 ; 196: 501-517
152. Steimer T., Driscoll P.. Divergent stress responses and coping styles in psychogenetically selected Roman high-(RLA) and low-(RLA) avoidance rats: Behavioural, neuroendocrine and developmental aspects. Stress. 2003 ; 6: 87-100
153. Steimer T., Driscoll P.. Inter-individual vs line/strain differences in psychogenetically selected Roman high-(RHA) and low-(RLA) avoidance rats: Neuroendocrine and behavioural aspects. Neuroscience & Biobehavioral Reviews. 2005 ; 29: 99-112
154. Stein D. J., Stahl S.. Serotonin and anxiety: Current models. International Clinical Psychopharmacology. 2000 ; 15 (Suppl. 2). S1 - S6
155. Strack F., Deutsch R.. Reflective and impulsive determinants of social behavior. Personality and Social Psychology Review. 2004 ; 8: 220-247
156. Strelau J.. The contribution of Pavlov's typology of CNS properties to personality research. European Psychologist. 1997 ; 2: 125-138
157. TellegenA.WallerN. G. (1992). Exploring personality through test construction: Development of the multidimensional personality questionnaire. Unpublished manuscript, University of Minnesota Press.
158. Thiel C. M., Müller C. P., Huston J. P., Schwarting R. K. W.. High versus low reactivity to a novel environment: Behavioural, pharmacological and neurochemical assessments. Neuroscience. 1999 ; 93: 243-251
159. Tollefson G. D., Rosenbaum J. F. Textbook of psychopharmacology. Schatzberg A. F. Nemeroff C. B., ed. Washington, DC: American Psychiatric Press ; 1998: 219-237.
160. Treit D.. Animal models for the study of anti-anxiety agents: A review. Neuroscience and Biobehavioral Reviews. 1985 ; 9: 203-222
161. Treit D., Menard J., Royan C.. Anxiogenic stimuli in the elevated plus-maze. Pharmacology, Biochemistry and Behavior. 1993 ; 44: 463-469
162. Ueno K. I., Togashi H., Mori K., Matsumoto M., Ohashi S., Hoshino A.,... Yoshioka M.. Behavioural and pharmacological relevance of stroke-prone spontaneously hypertensive rats as an animal model of a developmental disorder. Behavioural Pharmacology. 2002 ; 13: 1-13
163. van den Heuvel O. A., Veltman D. J., Groenewegen H. J., Cath D. C., van Balkom A. J. L. M., van Hartskamp J., van Dyck R.. Frontal-striatal dysfunction during planning in obsessive-compulsive disorder. Archives of General Psychiatry. 2005a ; 62: 301-310
164. van den Heuvel O. A., Veltman D. J., Groenewegen H. J., Witter M. P., Merkelbach J., Cath D. C., van Dyck R.. Disorder-specific neuroanatomical correlates of attentional bias in obsessive-compulsive disorder, panic disorder, and hypochondriasis. Archives of General Psychiatry. 2005b ; 62: 922-933
165. Vyas A., Chattarji S.. Modulation of different states of anxiety-like behavior by chronic stress. Behavioral Neuroscience. 2004 ; 118: 1450-1454
166. Wahlsten D., Metten P., Phillips T. J., Boehm S. L., Burkhart-Kasch S., Dorow J.,... Crabbe J. C.. Different data from different labs: Lessons from studies of gene-environment interaction. Journal of Neurobiology. 2003 ; 54: 283-311
167. Walf A. A., Frye C. A.. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nature Protocols. 2007 ; 2: 322-328
168. Weintraub D., Newberg A. B., Cary M. S., Siderowf A. D., Moberg P. J., Kleiner-Fisman G.,... Katz I. R.. Striatal dopamine transporter imaging correlates with anxiety and depression symptoms in Parkinson's disease. The Journal of Nuclear Medicine. 2005 ; 46: 227-232
169. Weiss S. M., Wadsworth G., Fletcher A., Dourish C. T.. Utility of
170. Wichers M., Maes M.. The psychoneuroimmuno-pathophysiology of cytokine-induced depression in humans. International Journal of Neuropsychopharmacology. 2002 ; 5: 375-388
171. Wigger A., Sánchez M. M., Mathys K. C., Ebner K., Frank E., Liu D.,... Landgraf R.. Alterations in central neuropeptide expression, release, and receptor binding in rats bred for high anxiety: Critical role of vasopressin. Neuropsychopharmacology. 2004 ; 29: 1-14
172. Willner P.. The validity of animal models of depression. Psychopharmacology. 1984 ; 83: 1-16
173. Willner P.. Validation criteria for animal models of human mental disorders: Learned helplessness as a paradigm case. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 1986 ; 10: 677-690
174. Willner P. Behavioural models in psychopharmacology: Theoretical, industrial and clinical perspectives. Willner P., ed. Cambridge, UK: Cambridge University Press ; 1991: 3-18.
175. Willner P., Mitchell P. J. Biological psychiatry. D'Haenen H. den Boer J. A. Willner P., ed. Chichester, UK: Wiley ; 2002: 703-726.
176. Woodcock J.. The prospects for "personalized medicine" in drug development and drug therapy. Journal of Clinical Pharmacy and Therapeutics. 2007 ; 81: 164-169
177. Wu J. C., Buchsbaum M. S., Hershey T. G., Hazlett E., Sicotte N., Johnson J. C.. PET in generalized anxiety disorder. Biological Psychiatry. 1991 ; 29: 1181-1199
178. Wu S. L., Hsu L. S., Tu W. T., Wang W. F., Huang Y. T., Pawlak C. R., Ho Y. J.. Effects of d-cycloserine on the behavior and ERK activity in the amygdala: Role of individual anxiety levels. Behavioural Brain Research. 2008 ; 187: 246-253
179. Yehuda R., Hyman S. E.. The impact of terrorism on brain, and behavior: What we know and what we need to know. Neuropsychopharmacology. 2005 ; 30: 1773-1780
180. Yerkes R. M., Yerkes A. W.. Nature and conditions of avoidance (fear) responses in chimpanzees. Journal of Comparative Psychology. 1936 ; 21: 53-66