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Middle-range exploratory activity in adult rats suggests higher resilience to chronic social defeat

Published online by Cambridge University Press:  16 December 2015

Denis Matrov ,
Kadri Kõiv ,
Margus Kanarik ,
Krista Peet ,
Karita Raudkivi  and
Jaanus Harro
Denis Matrov
Affiliation:
Department of Psychology, Estonian Centre of Behavioural and Health Sciences, Division of Neuropsychopharmacology, University of Tartu, Tartu, Estonia
Kadri Kõiv
Affiliation:
Department of Psychology, Estonian Centre of Behavioural and Health Sciences, Division of Neuropsychopharmacology, University of Tartu, Tartu, Estonia
Margus Kanarik
Affiliation:
Department of Psychology, Estonian Centre of Behavioural and Health Sciences, Division of Neuropsychopharmacology, University of Tartu, Tartu, Estonia
Krista Peet
Affiliation:
Department of Psychology, Estonian Centre of Behavioural and Health Sciences, Division of Neuropsychopharmacology, University of Tartu, Tartu, Estonia
Karita Raudkivi
Affiliation:
Department of Psychology, Estonian Centre of Behavioural and Health Sciences, Division of Neuropsychopharmacology, University of Tartu, Tartu, Estonia
Jaanus Harro*
Affiliation:
Department of Psychology, Estonian Centre of Behavioural and Health Sciences, Division of Neuropsychopharmacology, University of Tartu, Tartu, Estonia
*
Dr. Jaanus Harro, Department of Psychology, Estonian Centre of Behavioural and Health Sciences, Division of Neuropsychopharmacology, University of Tartu, Ravila 14A Chemicum, 50411 Tartu, Estonia. Tel: +372 7376657; Fax: +372 7375900; E-mail: [email protected]
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Abstract

Objective

Stressful life events play an important role in the aetiology of human mood disorders and are frequently modelled by chronic social defeat (SD) in rodents. Exploratory phenotype in rats is a stable trait that is likely related to inter-individual differences in reactivity to stress. The aim of the study was to confirm that low levels of exploratory activity (LE) are, in rodents, a risk factor for passive stress coping, and to clarify the role of medium (ME) and high (HE) exploratory disposition in the sensitivity to SD.

Methods

We examined the effect of SD on male Wistar rats with LE, ME, and HE activity levels as measured in the exploration box. After SD, the rats were evaluated in social preference, elevated zero maze, and open-field tests. Brain tissue levels of monoamines were measured by high-performance liquid chromatography.

Results

Rats submitted to SD exhibited lower weight gain, higher sucrose consumption, showed larger stress-induced hyperthermia, lower levels of homovanillic acid in the frontal cortex, and higher levels of noradrenaline in the amygdala and hippocampus. Open-field, elevated zero maze, and social preference tests revealed the interaction between stress and phenotype, as only LE-rats were further inhibited by SD. ME-rats exhibited the least reactivity to stress in terms of changes in body weight, stress-induced hyperthermia, and sucrose intake.

Conclusion

Both low and high novelty-related activity, especially the former, are associated with elevated sensitivity to social stress. This study shows that both tails of a behavioural dimension can produce stress-related vulnerability.

Keywords

depressionexploratory behaviourinter-individual differencessocial defeatvulnerability
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 28 , Issue 3 , June 2016 , pp. 125 - 140
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Copyright
© Scandinavian College of Neuropsychopharmacology 2015 

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References

1. Ferrari, AJ, Charlson, FJ, Norman, RE et al. Burden of depressive disorders by country, sex, age, and year: findings from the global burden of disease study 2010. PLoS Med 2013;10:e1001547.CrossRefGoogle ScholarPubMed
2. Kendler, KS, Thornton, LM, Gardner, CO. Stressful life events and previous episodes in the etiology of major depression in women: an evaluation of the ‘kindling’ hypothesis. Am J Psychiatry 2000;157:1243–1251.Google Scholar
3. Pacák, K, Palkovits, M. Stressor specificity of central neuroendocrine responses: implications for stress-related disorders. Endocr Rev 2001;22:502–548.CrossRefGoogle ScholarPubMed
4. Deakin, JF. 5-HT, antidepressant drugs and the psychosocial origins of depression. J Psychopharmacol 1996;10:31–38.Google Scholar
5. Shively, CA, Willard, SL. Behavioral and neurobiological characteristics of social stress versus depression in nonhuman primates. Exp Neurol 2012;233:87–94.Google Scholar
6. Kendler, KS, Hettema, JM, Butera, F, Gardner, CO, Prescott, CA. Life event dimensions of loss, humiliation, entrapment, and danger in the prediction of onsets of major depression and generalized anxiety. Arch Gen Psychiatry 2003;60:789–796.Google Scholar
7. Slavich, GM, Thornton, T, Torres, LD, Monroe, SM, Gotlib, IH. Targeted rejection predicts hastened onset of major depression. J Soc Clin Psychol 2009;28:223–243.Google Scholar
8. Koolhaas, JM, Coppens, CM, De Boer, SF, Buwalda, B, Meerlo, P, Timmermans, PJA. The resident-intruder paradigm: a standardized test for aggression, violence and social stress. J Vis Exp 2013;77:e4367.Google Scholar
9. Tidey, JW, Miczek, KA. Acquisition of cocaine self-administration after social stress: role of accumbens dopamine. Psychopharmacology (Berl) 1997;130:203–212.Google Scholar
10. Meerlo, P, Overkamp, G, Daan, S, Van Den Hoofdakker, R, Koolhaas, J. Changes in behaviour and body weight following a single or double social defeat in rats. Stress 1996;1:21–32.Google Scholar
11. Meerlo, P, Overkamp, GJF, Koolhaas, JM. Behavioural and physiological consequences of a single social defeat in Roman high- and low-avoidance rats. Psychoneuroendocrinology 1997;22:155–168.CrossRefGoogle ScholarPubMed
12. Meerlo, P, Overkamp, GJF, Benning, MA, Koolhaas, JM, van den Hoofdakker, RH. Long-term changes in open field behaviour following a single social defeat in rats can be reversed by sleep deprivation. Physiol Behav 1996;60:115–119.Google Scholar
13. Miczek, KA, Yap, JJ, Covington, III HE. Social stress, therapeutics and drug abuse: preclinical models of escalated and depressed intake. Pharmacol Ther 2008;120:102–128.CrossRefGoogle ScholarPubMed
14. Hollis, F, Kabbaj, M. Social defeat as an animal model for depression. ILAR J 2014;55:221–232.Google Scholar
15. Chaouloff, F. Social stress models in depression research: what do they tell us? Cell Tissue Res 2013;354:179–190.Google Scholar
16. Harro, J. Inter-individual differences in neurobiology as vulnerability factors for affective disorders: implications for psychopharmacology. Pharmacol Ther 2010;125:402–422.Google Scholar
17. Armario, A, Nadal, R. Individual differences and the characterization of animal models of psychopathology: a strong challenge and a good opportunity. Front Pharmacol 2013;4:137.Google Scholar
18. Otter, MH, Matto, V, Sõukand, R, Skrebuhhova, T, Allikmets, L, Harro, J. Characterization of rat exploratory behavior using the exploration box test. Methods Find Exp Clin Pharmacol 1997;19:683–691.Google ScholarPubMed
19. Mällo, T, Alttoa, A, Kõiv, K, Tõnissaar, M, Eller, M, Harro, J. Rats with persistently low or high exploratory activity: behaviour in tests of anxiety and depression, and extracellular levels of dopamine. Behav Brain Res 2007;177:269–281.CrossRefGoogle ScholarPubMed
20. Mällo, T, Kõiv, K, Koppel, I et al. Regulation of extracellular serotonin levels and brain-derived neurotrophic factor in rats with high and low exploratory activity. Brain Res 2008;1194:110–117.Google Scholar
21. Alttoa, A, Seeman, P, Kõiv, K, Eller, M, Harro, J. Rats with persistently high exploratory activity have both higher extracellular dopamine levels and higher proportion of D2 high receptors in the striatum. Synapse 2009;63:443–446.Google Scholar
22. Raudkivi, K, Alttoa, A, Leito, I, Harro, J. Differences in extracellular glutamate levels in striatum of rats with high and low exploratory activity. Pharmacol Rep 2015;67:858–865.CrossRefGoogle ScholarPubMed
23. Matrov, D, Vonk, A, Herm, L, Rinken, A, Harro, J. Activating effects of chronic variable stress in rats with different exploratory activity: association with dopamine D2 receptor function in nucleus accumbens. Neuropsychobiology 2011;64:110–122.Google Scholar
24. Pruus, K, Rudissaar, R, Skrebuhhova-Malmros, T, Allikmets, L, Matto, V. Development of apomorphine-induced aggressive behavior: comparison of adult male and female Wistar rats. Methods Find Exp Clin Pharmacol 2000;22:47–50.Google Scholar
25. Kanarik, M, Alttoa, A, Matrov, D et al. Brain responses to chronic social defeat stress: effects on regional oxidative metabolism as a function of a hedonic trait, and gene expression in susceptible and resilient rats. Eur Neuropsychopharmacol 2011;21:92–107.Google Scholar
26. Vinkers, CH, van Bogaert, MJV, Klanker, M et al. Translational aspects of pharmacological research into anxiety disorders: the stress-induced hyperthermia (SIH) paradigm. Eur J Pharmacol 2008;585:407–425.Google Scholar
27. Kõiv, K, Harro, J. Differences in 5-HT1A receptor-mediated hypothermia in rats with low or high exploratory activity. Behav Pharmacol 2010;21:765–768.CrossRefGoogle ScholarPubMed
28. Berton, O, Mcclung, CA, Dileone, RJ et al. Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science 2006;311:864–868.Google Scholar
29. Shepherd, JK, Grewal, SS, Fletcher, A, Bill, DJ, Dourish, CT. Behavioural and pharmacological characterisation of the elevated ‘zero-maze’ as an animal model of anxiety. Psychopharmacology (Berl) 1994;116:56–64.Google Scholar
30. Matto, V, Harro, J, Allikmets, L. The effects of cholecystokinin A and B receptor antagonists on exploratory behaviour in the elevated zero-maze in rat. Neuropharmacology 1997;36:389–396.Google Scholar
31. Porsolt, RD, Anton, G, Blavet, N, Jalfre, M. Behavioural despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol 1978;47:379–391.Google Scholar
32. Miczek, KA. A new test for aggression in rats without aversive stimulation: differential effects of d-amphetamine and cocaine. Psychopharmacology (Berl) 1979;60:253–259.Google Scholar
33. Blanchard, RJ, Blanchard, CD. Aggressive behavior in the rat. Behav Biol 1977;21:197–224.Google Scholar
34. Tornatzky, W, Miczek, KA. Behavioral and autonomic responses to intermittent social stress: differential protection by clonidine and metoprolol. Psychopharmacology (Berl) 1994;116:346–356.Google Scholar
35. Bhatnagar, S, Vining, C, Iyer, V, Kinni, V. Changes in hypothalamic-pituitary-adrenal function, body temperature, body weight and food intake with repeated social stress exposure in rats. J Neuroendocrinol 2006;18:13–24.Google Scholar
36. Tornatzky, W, Miczek, KA. Long-term impairment of autonomic circadian rhythms after brief intermittent social stress. Physiol Behav 1993;53:983–993.Google Scholar
37. Wood, SK, Walker, HE, Valentino, RJ, Bhatnagar, S. Individual differences in reactivity to social stress predict susceptibility and resilience to a depressive phenotype: role of corticotropin-releasing factor. Endocrinology 2010;151:1795–1805.Google Scholar
38. Sgoifo, A, Koolhaas, JM, Musso, E, de Boer, SF. Different sympathovagal modulation of heart rate during social and nonsocial stress episodes in wild-type rats. Physiol Behav 1999;67:733–738.Google Scholar
39. Razzoli, M, Carboni, L, Arban, R. Alterations of behavioral and endocrinological reactivity induced by 3 brief social defeats in rats: relevance to human psychopathology. Psychoneuroendocrinology 2009;34:1405–1416.Google Scholar
40. Becker, C, Zeau, B, Rivat, C, Blugeot, A, Hamon, M, Benoliel, J-J. Repeated social defeat-induced depression-like behavioral and biological alterations in rats: involvement of cholecystokinin. Mol Psychiatry 2008;13:1079–1092.Google Scholar
41. Rygula, R, Abumaria, N, Flügge, G, Fuchs, E, Rüther, E, Havemann-Reinecke, U. Anhedonia and motivational deficits in rats: impact of chronic social stress. Behav Brain Res 2005;162:127–134.Google Scholar
42. Nakayasu, T, Ishii, K. Effects of pair-housing after social defeat experience on elevated plus-maze behavior in rats. Behav Processes 2008;78:477–480.Google Scholar
43. Pearson, BL, Blanchard, DC, Blanchard, RJ. Social stress effects on defensive behavior and anxiety. In Conrad CD editor The handbook of stress: neuropsychological effects on the brain. Oxford, UK: Wiley-Blackwell, 2011; p. 367–387.Google Scholar
44. Miczek, KA, Nikulina, EM, Shimamoto, A, Covington, HE. Escalated or suppressed cocaine reward, tegmental BDNF, and accumbal dopamine caused by episodic versus continuous social stress in rats. J Neurosci 2011;31:9848–9857.Google Scholar
45. Hollis, F, Wang, H, Dietz, D, Gunjan, A, Kabbaj, M. The effects of repeated social defeat on long-term depressive-like behavior and short-term histone modifications in the hippocampus in male Sprague-Dawley rats. Psychopharmacology (Berl) 2010;211:69–77.Google Scholar
46. Harro, J, Tõnissaar, M, Eller, M, Kask, A, Oreland, L. Chronic variable stress and 5-HT denervation by parachloroamphetamine treatment in the rat: effects on behavior and monoamine neurochemistry. Brain Res 2001;899:227–239.Google Scholar
47. Wurtman, RJ, Wurtman, JJ. Brain serotonin, carbohydrate-craving, obesity and depression. Obes Res Suppl 1995;4:477S–480S.Google Scholar
48. Tõnissaar, M, Mällo, T, Eller, M, Häidkind, R, Kõiv, K, Harro, J. Rat behavior after chronic variable stress and partial lesioning of the 5-HT-ergic neurotransmission: effects of citalopram. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:164–177.Google Scholar
49. Moles, A, Bartolomucci, A, Garbugino, L et al. Psychosocial stress affects energy balance in mice: modulation by social status. Psychoneuroendocrinology 2006;31:623–633.CrossRefGoogle ScholarPubMed
50. Hayashida, S, Oka, T, Mera, T, Tsuji, S. Repeated social defeat stress induces chronic hyperthermia in rats. Physiol Behav 2010;101:124–131.Google Scholar
51. Lang, A, Harro, J, Soosaar, A et al. Role of N-methyl-d-aspartic acid and cholecystokinin receptors in apomorphine-induced aggressive behaviour in rats. Naunyn Schmiedebergs Arch Pharmacol 1995;351:363–370.Google Scholar
52. Ruis, MAW, Te Brake, JHA, Buwalda, B et al. Housing familiar male wildtype rats together reduces the long-term adverse behavioural and physiological effects of social defeat. Psychoneuroendocrinology 1999;24:285–300.Google Scholar
53. Heinrichs, SC, Pich, EM, Miczek, KA, Britton, KT, Koob, GF. Corticotropin-releasing factor antagonist reduces emotionality in socially defeated rats via direct neurotropic action. Brain Res 1992;581:190–197.Google Scholar
54. Piazza, PV, Deminiere, J-M, Le Moal, M, Simon, H. Factors that predict individual vulnerability to amphetamine self-administration. Science 1989;245:1511–1513.Google Scholar
55. Dellu, F, Piazza, PV, Mayo, W, Le Moal, M, Simon, H. Novelty-seeking in rats – biobehavioral characteristics and possible relationship with the sensation-seeking trait in man. Neuropsychobiology 1996;34:136–145.Google Scholar
56. Kabbaj, M, Devine, D, Savage, V, Akil, H. Neurobiological correlates of individual differences in novelty-seeking behavior in the rat: differential expression of stress-related molecules. J Neurosci 2000;20:6983–6988.CrossRefGoogle ScholarPubMed
57. Duclot, F, Hollis, F, Darcy, MJ, Kabbaj, M. Individual differences in novelty-seeking behavior in rats as a model for psychosocial stress-related mood disorders. Physiol Behav 2011;104:296–305.Google Scholar
58. Calvo, N, Cecchi, M, Kabbaj, M, Watson, SJ, Akil, H. Differential effects of social defeat in rats with high and low locomotor response to novelty. Neuroscience 2011;183:81–89.Google Scholar
59. Abercrombie, ED, Jacobs, BL. Single-unit response of noradrenergic neurons in the locus coeruleus of freely moving cats. II. Adaptation to chronically presented stressful stimuli. J Neurosci 1987;7:2844–2848.Google Scholar
60. Harro, J, Oreland, L. Depression as a spreading adjustment disorder of monoaminergic neurons: a case for primary implication of the locus coeruleus. Brain Res Rev 2001;38:79–128.Google Scholar
61. Abercrombie, E, Keller, R Jr., Zigmond, M. Characterization of hippocampal norepinephrine release as measured by microdialysis perfusion: pharmacological and behavioral studies. Neuroscience 1988;27:897–904.Google Scholar
62. Tanaka, T, Yokoo, H, Mizoguchi, K, Yoshida, M, Tsuda, A, Tanaka, M. Noradrenaline release in the rat amygdala is increased by stress: studies with intracerebral microdialysis. Brain Res 1991;544:174–176.CrossRefGoogle ScholarPubMed
63. Haenisch, B, Bilkei-Gorzo, A, Caron, MG, Bönisch, H. Knockout of the norepinephrine transporter and pharmacologically diverse antidepressants prevent behavioral and brain neurotrophin alterations in two chronic stress models of depression. J Neurochem 2009;111:403–416.CrossRefGoogle ScholarPubMed
64. Hill, MN, Hellemans, KGC, Verma, P, Gorzalka, BB, Weinberg, J. Neurobiology of chronic mild stress: parallels to major depression. Neurosci Biobehav Rev 2012;36:2085–2117.Google Scholar
65. Puglisi-Allegra, S, Cabib, S. Effects of defeat experiences on dopamine metabolism in different brain areas of the mouse. Aggress Behav 1990;16:271–284.Google Scholar
66. Strekalova, T, Couch, Y, Kholod, N et al. Update in the methodology of the chronic stress paradigm: internal control matters. Behav Brain Funct 2011;7:9.Google Scholar
67. Harro, J, Kanarik, M, Kaart, T et al. Revealing the cerebral regions and networks mediating vulnerability to depression: oxidative metabolism mapping of rat brain. Behav Brain Res 2014;267:83–94.Google Scholar
68. Kessler, RC, Petukhova, M, Sampson, NA, Zaslavsky, AM, Wittchen, H-U. Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. Int J Methods Psychiatr Res 2012;21:169–184.Google Scholar