Environmental enrichment effects after early stress on behavior and functional brain networks in adult rats

Autoři: Héctor González-Pardo aff001;  Jorge L. Arias aff001;  Guillermo Vallejo aff002;  Nélida M. Conejo aff001
Působiště autorů: Laboratory of Neuroscience, Department of Psychology and Institute of Neuroscience of the Principality of Asturias (INEUROPA), University of Oviedo, Oviedo, Spain aff001;  Methodology Area, Department of Psychology and Institute of Neuroscience of the Principality of Asturias (INEUROPA), University of Oviedo, Oviedo, Spain aff002
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0226377


Early life stress is associated with long-term and pervasive adverse effects on neuroendocrine development, affecting normal cognitive and emotional development. Experimental manipulations like environmental enrichment (EE) may potentially reverse the effects of early life stress induced by maternal separation (MS) paradigm in rodents. However, the functional brain networks involved in the effects of EE after prolonged exposure to MS have not yet been investigated. In order to evaluate possible changes in brain functional connectivity induced by EE after MS, quantitative cytochrome c oxidase (CCO) histochemistry was applied to determine regional brain oxidative metabolism in adult male rats. Unexpectedly, results show that prolonged MS during the entire weaning period did not cause any detrimental effects on spatial learning and memory, including depressive-like behavior evaluated in the forced-swim test, and decreased anxiety-like behavior. However, EE seemed to alter anxiety- and depression-like behaviors in both control and MS groups, but improved spatial memory in the latter groups. Analysis of brain CCO activity showed significantly lower metabolic capacity in most brain regions selected in EE groups probably associated with chronic stress, but no effects of MS on brain metabolic capacity. In addition, principal component analysis of CCO activity revealed increased large-scale functional brain connectivity comprising at least three main networks affected by EE in both MS and control groups. Moreover, EE induced a pattern of functional brain connectivity associated with stress and anxiety-like behavior as compared with non-enriched groups. In conclusion, EE had differential effects on cognition and emotional behavior irrespective of exposure to MS. In view of the remarkable effects of EE on brain function and behavior, implementation of rodent housing conditions should be optimized by evaluating the balance between scientific validity and animal welfare.

Klíčová slova:

Animal behavior – Behavior – Collective animal behavior – Depression – principal component analysis – Psychological stress – Rats – Spatial memory


1. Ventriglio A, Gentile A, Baldessarini RJ, Bellomo A. Early-life stress and psychiatric disorders: epidemiology, neurobiology and innovative pharmacological targets. Curr Pharm Des. 2015;21: 1379–87. Available: http://www.ncbi.nlm.nih.gov/pubmed/25564392 doi: 10.2174/1381612821666150105121244 25564392

2. Carr CP, Martins CMS, Stingel AM, Lemgruber VB, Juruena MF. The Role of Early Life Stress in Adult Psychiatric Disorders. J Nerv Ment Dis. 2013;201: 1007–1020. doi: 10.1097/NMD.0000000000000049 24284634

3. Nemeroff CB. Paradise Lost: The Neurobiological and Clinical Consequences of Child Abuse and Neglect. Neuron. 2016;89: 892–909. doi: 10.1016/j.neuron.2016.01.019 26938439

4. Schmidt M V., Wang X-D, Meijer OC. Early life stress paradigms in rodents: potential animal models of depression? Psychopharmacology (Berl). 2011;214: 131–140. doi: 10.1007/s00213-010-2096-0 21086114

5. van Bodegom M, Homberg JR, Henckens MJAG. Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure. Front Cell Neurosci. 2017;11: 87. doi: 10.3389/fncel.2017.00087 28469557

6. Lippmann M, Bress A, Nemeroff CB, Plotsky PM, Monteggia LM. Long-term behavioural and molecular alterations associated with maternal separation in rats. Eur J Neurosci. France; 2007;25: 3091–3098. doi: 10.1111/j.1460-9568.2007.05522.x 17561822

7. González-Pardo H, Arias JL, Vallejo G, Conejo NM. Influence of environmental enrichment on the volume of brain regions sensitive to early life stress by maternal separation in rats. Psicothema. 2019;31: 46–52. doi: 10.7334/psicothema2018.290 30664410

8. Li M, Xue X, Shao S, Shao F, Wang W. Cognitive, emotional and neurochemical effects of repeated maternal separation in adolescent rats. Brain Res. Netherlands; 2013;1518: 82–90. doi: 10.1016/j.brainres.2013.04.026 23623774

9. Colorado RA, Shumake J, Conejo NM, Gonzalez-Pardo H, Gonzalez-Lima F. Effects of maternal separation, early handling, and standard facility rearing on orienting and impulsive behavior of adolescent rats. Behav Processes. 2006;71. doi: 10.1016/j.beproc.2006.09.015

10. Maghami S, Zardooz H, Khodagholi F, Binayi F, Ranjbar Saber R, Hedayati M, et al. Maternal separation blunted spatial memory formation independent of peripheral and hippocampal insulin content in young adult male rats. PLoS One. United States; 2018;13: e0204731. doi: 10.1371/journal.pone.0204731 30332425

11. Daniels WMU, Pietersen CY, Carstens ME, Stein DJ. Maternal separation in rats leads to anxiety-like behavior and a blunted ACTH response and altered neurotransmitter levels in response to a subsequent stressor. Metab Brain Dis. United States; 2004;19: 3–14.

12. Zalosnik MI, Pollano A, Trujillo V, Suárez MM, Durando PE. Effect of maternal separation and chronic stress on hippocampal-dependent memory in young adult rats: evidence for the match-mismatch hypothesis. Stress. 2014;17: 445–450. doi: 10.3109/10253890.2014.936005 24930801

13. Kambali MY, Anshu K, Kutty BM, Muddashetty RS, Laxmi TR. Effect of early maternal separation stress on attention, spatial learning and social interaction behaviour. Exp Brain Res. 2019; doi: 10.1007/s00221-019-05567-2 31154461

14. Murthy S, Gould E. Early Life Stress in Rodents: Animal Models of Illness or Resilience? Front Behav Neurosci. 2018;12: 157. doi: 10.3389/fnbeh.2018.00157 30108490

15. Tractenberg SG, Levandowski ML, de Azeredo LA, Orso R, Roithmann LG, Hoffmann ES, et al. An overview of maternal separation effects on behavioural outcomes in mice: Evidence from a four-stage methodological systematic review. Neurosci Biobehav Rev. 2016;68: 489–503. doi: 10.1016/j.neubiorev.2016.06.021 27328784

16. Francis DD, Diorio J, Plotsky PM, Meaney MJ. Environmental enrichment reverses the effects of maternal separation on stress reactivity. J Neurosci. 2002;22: 7840–3. Available: http://www.ncbi.nlm.nih.gov/pubmed/12223535 doi: 10.1523/JNEUROSCI.22-18-07840.2002 12223535

17. Simpson J, Kelly JP. The impact of environmental enrichment in laboratory rats—Behavioural and neurochemical aspects. Behav Brain Res. 2011;222: 246–264. doi: 10.1016/j.bbr.2011.04.002 21504762

18. Hoffmann A, Spengler D. The Mitochondrion as Potential Interface in Early-Life Stress Brain Programming. Front Behav Neurosci. 2018;12: 306. doi: 10.3389/fnbeh.2018.00306 30574076

19. Picard M, McEwen BS, Epel ES, Sandi C. An energetic view of stress: Focus on mitochondria. Front Neuroendocrinol. 2018;49: 72–85. doi: 10.1016/j.yfrne.2018.01.001 29339091

20. Picard M, McEwen BS. Psychological Stress and Mitochondria. Psychosom Med. 2018;80: 126–140. doi: 10.1097/PSY.0000000000000544 29389735

21. Gonzalez-Lima F, Cada A. Cytochrome oxidase activity in the auditory system of the mouse: a qualitative and quantitative histochemical study. Neuroscience. 1994;63: 559–78. Available: http://www.ncbi.nlm.nih.gov/pubmed/7891865 doi: 10.1016/0306-4522(94)90550-9 7891865

22. Spivey JM, Padilla E, Shumake JD, Gonzalez-Lima F. Effects of maternal separation, early handling, and gonadal sex on regional metabolic capacity of the preweanling rat brain. Brain Res. 2011;1367: 198–206. doi: 10.1016/j.brainres.2010.10.038 20969837

23. Banqueri M, Méndez M, Arias JL. Spatial memory-related brain activity in normally reared and different maternal separation models in rats. Physiol Behav. 2017;181: 80–85. doi: 10.1016/j.physbeh.2017.09.007 28893662

24. Sampedro-Piquero P, Zancada-Menendez C, Begega A, Rubio S, Arias JL. Effects of environmental enrichment on anxiety responses, spatial memory and cytochrome c oxidase activity in adult rats. Brain Res Bull. 2013;98: 1–9. doi: 10.1016/j.brainresbull.2013.06.006 23831916

25. Sampedro-Piquero P, Begega A, Zancada-Menendez C, Cuesta M, Arias JL. Age-dependent effects of environmental enrichment on brain networks and spatial memory in Wistar rats. Neuroscience. 2013;248: 43–53. doi: 10.1016/j.neuroscience.2013.06.003 23769820

26. Hui J-J, Zhang Z-J, Liu S-S, Xi G-J, Zhang X-R, Teng G-J, et al. Hippocampal neurochemistry is involved in the behavioural effects of neonatal maternal separation and their reversal by post-weaning environmental enrichment: a magnetic resonance study. Behav Brain Res. 2011;217: 122–7. doi: 10.1016/j.bbr.2010.10.014 20974193

27. Vivinetto AL, Suárez MM, Rivarola MA. Neurobiological effects of neonatal maternal separation and post-weaning environmental enrichment. Behav Brain Res. 2013;240: 110–8. doi: 10.1016/j.bbr.2012.11.014 23195113

28. Dandi Ε, Kalamari A, Touloumi O, Lagoudaki R, Nousiopoulou E, Simeonidou C, et al. Beneficial effects of environmental enrichment on behavior, stress reactivity and synaptophysin/BDNF expression in hippocampus following early life stress. Int J Dev Neurosci. 2018;67: 19–32. doi: 10.1016/j.ijdevneu.2018.03.003 29545098

29. Slattery DA, Cryan JF. Using the rat forced swim test to assess antidepressant-like activity in rodents. Nat Protoc. 2012;7: 1009–1014. doi: 10.1038/nprot.2012.044 22555240

30. Singh K, Bishnoi M, Kulkarni SK. Elevated Zero-maze: A paradigm to evaluate anti-anxiety effects of drugs. Methods Find Exp Clin Pharmacol. 2007;29: 343. doi: 10.1358/mf.2007.29.5.1117557 17805436

31. Heredia L, Torrente M, Domingo JL, Colomina MT. Individual housing and handling procedures modify anxiety levels of Tg2576 mice assessed in the zero maze test. Physiol Behav. 2012;107: 187–191. doi: 10.1016/j.physbeh.2012.06.021 22776622

32. Mendez-Couz M, Conejo NM, Gonzalez-Pardo H, Arias JL. Functional interactions between dentate gyrus, striatum and anterior thalamic nuclei on spatial memory retrieval. Brain Res. 2015;1605. doi: 10.1016/j.brainres.2015.02.005 25680583

33. Vorhees C V, Williams MT. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc. 2006;1: 848–858. doi: 10.1038/nprot.2006.116 17406317

34. Méndez-Couz M, González-Pardo H, Vallejo G, Arias JL, Conejo NM. Spatial memory extinction differentially affects dorsal and ventral hippocampal metabolic activity and associated functional brain networks. Hippocampus. 2016;26. doi: 10.1002/hipo.22602 27102086

35. González-Pardo H, Conejo NM, Lana G, Arias JL. Different brain networks underlying the acquisition and expression of contextual fear conditioning: A metabolic mapping study. Neuroscience. 2012;202. doi: 10.1016/j.neuroscience.2011.11.064 22173014

36. Cantacorps L, González-Pardo H, Arias JL, Valverde O, Conejo NM. Altered brain functional connectivity and behaviour in a mouse model of maternal alcohol binge-drinking. Prog Neuro-Psychopharmacology Biol Psychiatry. Elsevier; 2018;84: 237–249. doi: 10.1016/J.PNPBP.2018.03.006 29526773

37. Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates: Hard Cover Edition. Elsevier Science; 2013.

38. Benjamini Y, Hochberg Y. Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing [Internet]. Journal of the Royal Statistical Society. Series B (Methodological). WileyRoyal Statistical Society; 1995. pp. 289–300. doi: 10.2307/2346101

39. Vallejo G, Fernández MP, Livacic-Rojas PE, Tuero-Herrero E. Comparison of Modern Methods for Analyzing Repeated Measures Data With Missing Values. Multivariate Behav Res. 2011;46: 900–937. doi: 10.1080/00273171.2011.625320 26736117

40. Cruz AP, Frei F, Graeff FG. Ethopharmacological analysis of rat behavior on the elevated plus-maze. Pharmacol Biochem Behav. 1994;49: 171–6. Available: http://www.ncbi.nlm.nih.gov/pubmed/7816869 doi: 10.1016/0091-3057(94)90472-3 7816869

41. Rodgers RJ, Johnson NJ. Factor analysis of spatiotemporal and ethological measures in the murine elevated plus-maze test of anxiety. Pharmacol Biochem Behav. 1995;52: 297–303. Available: http://www.ncbi.nlm.nih.gov/pubmed/8577794 doi: 10.1016/0091-3057(95)00138-m 8577794

42. Weiss SM, Wadsworth G, Fletcher A, Dourish CT. Utility of ethological analysis to overcome locomotor confounds in elevated maze models of anxiety. Neurosci Biobehav Rev. 1998;23: 265–71. Available: http://www.ncbi.nlm.nih.gov/pubmed/9884119 doi: 10.1016/s0149-7634(98)00027-x 9884119

43. Wang Q, Li M, Du W, Shao F, Wang W. The different effects of maternal separation on spatial learning and reversal learning in rats. Behav Brain Res. 2015;280: 16–23. doi: 10.1016/j.bbr.2014.11.040 25479401

44. Roque S, Mesquita AR, Palha JA, Sousa N, Correia-Neves M. The Behavioral and Immunological Impact of Maternal Separation: A Matter of Timing. Front Behav Neurosci. Frontiers; 2014;8: 192. doi: 10.3389/fnbeh.2014.00192 24904343

45. Schmidt M V., Wang X-D, Meijer OC. Early life stress paradigms in rodents: potential animal models of depression? Psychopharmacology (Berl). 2011;214: 131–140. doi: 10.1007/s00213-010-2096-0 21086114

46. Roman E, Gustafsson L, Berg M, Nylander I. Behavioral profiles and stress-induced corticosteroid secretion in male Wistar rats subjected to short and prolonged periods of maternal separation. Horm Behav. Academic Press; 2006;50: 736–747. doi: 10.1016/j.yhbeh.2006.06.016 16876800

47. Ploj K, Roman E, Nylander I. Effects of maternal separation on brain nociceptin/orphanin FQ peptide levels in male Wistar rats. Pharmacol Biochem Behav. 2002;73: 123–9. Available: http://www.ncbi.nlm.nih.gov/pubmed/12076731 doi: 10.1016/s0091-3057(02)00778-5 12076731

48. Estanislau C, Morato S. Prenatal stress produces more behavioral alterations than maternal separation in the elevated plus-maze and in the elevated T-maze. Behav Brain Res. 2005;163: 70–77. doi: 10.1016/j.bbr.2005.04.003 15941599

49. Macrì S, Chiarotti F, Würbel H. Maternal separation and maternal care act independently on the development of HPA responses in male rats. Behav Brain Res. 2008;191: 227–34. doi: 10.1016/j.bbr.2008.03.031 18468700

50. Arnett MG, Pan MS, Doak W, Cyr PEP, Muglia LM, Muglia LJ. The role of glucocorticoid receptor-dependent activity in the amygdala central nucleus and reversibility of early-life stress programmed behavior. Transl Psychiatry. 2015;5: e542. doi: 10.1038/tp.2015.35 25849981

51. Rodgers RJ, Dalvi A. Anxiety, defence and the elevated plus-maze. Neurosci Biobehav Rev. 1997;21: 801–10. Available: http://www.ncbi.nlm.nih.gov/pubmed/9415905 doi: 10.1016/s0149-7634(96)00058-9 9415905

52. Roy V, Chapillon P. Further evidences that risk assessment and object exploration behaviours are useful to evaluate emotional reactivity in rodents. Behav Brain Res. 2004;154: 439–448. doi: 10.1016/j.bbr.2004.03.010 15313032

53. Cole JC, Rodgers RJ. Ethological evaluation of the effects of acute and chronic buspirone treatment in the murine elevated plus-maze test: comparison with haloperidol. Psychopharmacology (Berl). 1994;114: 288–96. Available: http://www.ncbi.nlm.nih.gov/pubmed/7838922

54. Nederhof E, Schmidt M V. Mismatch or cumulative stress: toward an integrated hypothesis of programming effects. Physiol Behav. 2012;106: 691–700. doi: 10.1016/j.physbeh.2011.12.008 22210393

55. Santarelli S, Zimmermann C, Kalideris G, Lesuis SL, Arloth J, Uribe A, et al. An adverse early life environment can enhance stress resilience in adulthood. Psychoneuroendocrinology. 2017;78: 213–221. doi: 10.1016/j.psyneuen.2017.01.021 28219813

56. Daskalakis NP, Oitzl MS, Schächinger H, Champagne DL, de Kloet ER. Testing the cumulative stress and mismatch hypotheses of psychopathology in a rat model of early-life adversity. Physiol Behav. 2012;106: 707–21. doi: 10.1016/j.physbeh.2012.01.015 22306534

57. Banqueri M, Méndez M, Arias JL. Behavioral effects in adolescence and early adulthood in two length models of maternal separation in male rats. Behav Brain Res. 2017;324: 77–86. doi: 10.1016/j.bbr.2017.02.006 28185885

58. Cao X, Huang S, Cao J, Chen T, Zhu P, Zhu R, et al. The timing of maternal separation affects morris water maze performance and long-term potentiation in male rats. Dev Psychobiol. 2014;56: 1102–1109. doi: 10.1002/dev.21130 23712516

59. Clinton SM, Watson SJ, Akil H. High novelty-seeking rats are resilient to negative physiological effects of the early life stress. Stress. 2014;17: 97–107. doi: 10.3109/10253890.2013.850670 24090131

60. Couto FS do, Batalha VL, Valadas JS, Data-Franca J, Ribeiro JA, Lopes L V. Escitalopram improves memory deficits induced by maternal separation in the rat. Eur J Pharmacol. 2012;695: 71–5. doi: 10.1016/j.ejphar.2012.08.020 22981666

61. Peña CJ, Nestler EJ, Bagot RC. Environmental Programming of Susceptibility and Resilience to Stress in Adulthood in Male Mice. Front Behav Neurosci. 2019;13: 40. doi: 10.3389/fnbeh.2019.00040 30881296

62. Sampedro-Piquero P, Álvarez-Suárez P, Moreno-Fernández RD, García-Castro G, Cuesta M, Begega A. Environmental Enrichment Results in Both Brain Connectivity Efficiency and Selective Improvement in Different Behavioral Tasks. Neuroscience. 2018;388: 374–383. doi: 10.1016/j.neuroscience.2018.07.036 30086366

63. Moncek F, Duncko R, Johansson BB, Jezova D. Effect of Environmental Enrichment on Stress Related Systems in Rats. J Neuroendocrinol. 2004;16: 423–431. doi: 10.1111/j.1365-2826.2004.01173.x 15117335

64. Schrijver NCA, Bahr NI, Weiss IC, Würbel H. Dissociable effects of isolation rearing and environmental enrichment on exploration, spatial learning and HPA activity in adult rats. Pharmacol Biochem Behav. 2002;73: 209–24. Available: http://www.ncbi.nlm.nih.gov/pubmed/12076740 doi: 10.1016/s0091-3057(02)00790-6 12076740

65. Crofton EJ, Zhang Y, Green TA. Inoculation stress hypothesis of environmental enrichment. Neurosci Biobehav Rev. 2015;49: 19–31. doi: 10.1016/j.neubiorev.2014.11.017 25449533

66. Green TA, Alibhai IN, Roybal CN, Winstanley CA, Theobald DEH, Birnbaum SG, et al. Environmental enrichment produces a behavioral phenotype mediated by low cyclic adenosine monophosphate response element binding (CREB) activity in the nucleus accumbens. Biol Psychiatry. 2010;67: 28–35. doi: 10.1016/j.biopsych.2009.06.022 19709647

67. Häidkind R, Eller M, Harro M, Kask A, Rinken A, Oreland L, et al. Effects of partial locus coeruleus denervation and chronic mild stress on behaviour and monoamine neurochemistry in the rat. Eur Neuropsychopharmacol. 2003;13: 19–28. doi: 10.1016/s0924-977x(02)00076-7 12480118

68. Harro J. Long-term partial 5-HT depletion: interference of anxiety and impulsivity? Psychopharmacology (Berl). 2002;164: 433–4. doi: 10.1007/s00213-002-1265-1 12457276

69. Porsolt RD, Bertin A, Jalfre M. “Behavioural despair” in rats and mice: Strain differences and the effects of imipramine. Eur J Pharmacol. 1978;51: 291–294. doi: 10.1016/0014-2999(78)90414-4 568552

70. Borsini F, Volterra G, Meli A. Does the behavioral “despair” test measure “despair”? Physiol Behav. 1986;38: 385–386. doi: 10.1016/0031-9384(86)90110-1 3786519

71. De Kloet ER, Molendijk ML. Coping with the Forced Swim Stressor: Towards Understanding an Adaptive Mechanism. Neural Plasticity. Hindawi Limited; 2016. doi: 10.1155/2016/6503162 27034848

72. Sandi C, Pinelo-Nava MT. Stress and memory: Behavioral effects and neurobiological mechanisms. Neural Plasticity. Hindawi Publishing Corporation; 2007. doi: 10.1155/2007/78970 18060012

73. Mumtaz F, Khan MI, Zubair M, Dehpour AR. Neurobiology and consequences of social isolation stress in animal model—A comprehensive review. Biomed Pharmacother. Elsevier Masson; 2018;105: 1205–1222. doi: 10.1016/j.biopha.2018.05.086 30021357

74. Zorzo C, Méndez-López M, Méndez M, Arias JL. Adult social isolation leads to anxiety and spatial memory impairment: Brain activity pattern of COx and c-Fos. Behav Brain Res. 2019;365: 170–177. doi: 10.1016/j.bbr.2019.03.011 30851318

75. Sharp JL, Zammit TG, Azar TA, Lawson DM. Stress-like responses to common procedures in male rats housed alone or with other rats. Contemp Top Lab Anim Sci. 2002;41: 8–14. Available: http://www.ncbi.nlm.nih.gov/pubmed/12109891

76. Barker TH, George RP, Howarth GS, Whittaker AL. Assessment of housing density, space allocation and social hierarchy of laboratory rats on behavioural measures of welfare. Homberg J, editor. PLoS One. 2017;12: e0185135. doi: 10.1371/journal.pone.0185135 28926644

77. Brenes JC, Lackinger M, Höglinger GU, Schratt G, Schwarting RKW, Wöhr M. Differential effects of social and physical environmental enrichment on brain plasticity, cognition, and ultrasonic communication in rats. J Comp Neurol. 2016;524: 1586–1607. doi: 10.1002/cne.23842 26132842

78. Leger M, Bouet V, Freret T, Darmaillacq A-S, Dacher M, Dauphin F, et al. Environmental enrichment improves recent but not remote memory in association with a modified brain metabolic activation profile in adult mice. Behav Brain Res. 2012;228: 22–9. doi: 10.1016/j.bbr.2011.11.022 22138509

79. Kanarik M, Alttoa A, Matrov D, Kõiv K, Sharp T, Panksepp J, 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. doi: 10.1016/j.euroneuro.2010.06.015 20656462

80. Mällo T, Matrov D, Kõiv K, Harro J. Effect of chronic stress on behavior and cerebral oxidative metabolism in rats with high or low positive affect. Neuroscience. 2009;164: 963–974. doi: 10.1016/j.neuroscience.2009.08.041 19706319

81. Harro J, Kanarik M, Kaart T, Matrov D, Kõiv K, Mällo T, et al. Revealing the cerebral regions and networks mediating vulnerability to depression: Oxidative metabolism mapping of rat brain. Behav Brain Res. Elsevier; 2014;267: 83–94. doi: 10.1016/j.bbr.2014.03.019 24662150

82. McCoy CR, Sabbagh MN, Huaman JP, Pickrell AM, Clinton SM. Oxidative metabolism alterations in the emotional brain of anxiety-prone rats. Prog Neuro-Psychopharmacology Biol Psychiatry. Elsevier BV; 2019;95: 109706. doi: 10.1016/j.pnpbp.2019.109706 31330216

83. McCoy CR, Golf SR, Melendez-Ferro M, Perez-Costas E, Glover ME, Jackson NL, et al. Altered metabolic activity in the developing brain of rats predisposed to high versus low depression-like behavior. Neuroscience. Elsevier Ltd; 2016;324: 469–484. doi: 10.1016/j.neuroscience.2016.03.014 26979051

84. Holper L, Lan MJ, Brown PJ, Sublette EM, Burke A, Mann JJ. Brain cytochrome-c-oxidase as a marker of mitochondrial function: A pilot study in major depression using NIRS. Depress Anxiety. 2019;36: 766–779. doi: 10.1002/da.22913 31111623

85. Videbech P. PET measurements of brain glucose metabolism and blood flow in major depressive disorder: A critical review. Acta Psychiatrica Scandinavica. 2000. pp. 11–20. doi: 10.1034/j.1600-0447.2000.101001011.x 10674946

86. Harro J, Kanarik M, Matrov D, Panksepp J. Mapping patterns of depression-related brain regions with cytochrome oxidase histochemistry: Relevance of animal affective systems to human disorders, with a focus on resilience to adverse events. Neuroscience and Biobehavioral Reviews. 2011. pp. 1876–1889. doi: 10.1016/j.neubiorev.2011.02.016 21382409

87. Hollis F, Van Der Kooij MA, Zanoletti O, Lozano L, Cantó C, Sandi C. Mitochondrial function in the brain links anxiety with social subordination. Proc Natl Acad Sci U S A. National Academy of Sciences; 2015;112: 15486–15491. doi: 10.1073/pnas.1512653112 26621716

88. Van Laeken N, Pauwelyn G, Dockx R, Descamps B, Brans B, Peremans K, et al. Regional alterations of cerebral [18F]FDG metabolism in the chronic unpredictable mild stress- and the repeated corticosterone depression model in rats. J Neural Transm. 2018;125: 1381–1393. doi: 10.1007/s00702-018-1899-8 29955973

89. Nestler EJ, Carlezon WA. The Mesolimbic Dopamine Reward Circuit in Depression. Biological Psychiatry. 2006. pp. 1151–1159. doi: 10.1016/j.biopsych.2005.09.018 16566899

90. Daviu N, Bruchas MR, Moghaddam B, Sandi C, Beyeler A. Neurobiological links between stress and anxiety. Neurobiol Stress. Elsevier BV; 2019;11: 100191. doi: 10.1016/j.ynstr.2019.100191 31467945

91. Lüthi A, Lüscher C. Pathological circuit function underlying addiction and anxiety disorders. Nature Neuroscience. Nature Publishing Group; 2014. pp. 1635–1643. doi: 10.1038/nn.3849 25402855

92. Sale A. A Systematic Look at Environmental Modulation and Its Impact in Brain Development. Trends Neurosci. 2018;41: 4–17. doi: 10.1016/j.tins.2017.10.004 29128107

93. Friston KJ, Frith CD, Liddle PF, Frackowiak RSJ. Functional Connectivity: The Principal-Component Analysis of Large (PET) Data Sets. J Cereb Blood Flow Metab. 1993;13: 5–14. doi: 10.1038/jcbfm.1993.4 8417010

94. Méndez-Couz M, Conejo NM, Vallejo G, Arias JL. Brain functional network changes following Prelimbic area inactivation in a spatial memory extinction task. Behav Brain Res. 2015;287: 247–255. doi: 10.1016/j.bbr.2015.03.033 25813749

95. Conejo NM, Cimadevilla JM, González-Pardo H, Méndez-Couz M, Arias JL. Hippocampal Inactivation with TTX Impairs Long-Term Spatial Memory Retrieval and Modifies Brain Metabolic Activity. PLoS One. 2013;8. doi: 10.1371/journal.pone.0064749 23724089

96. Conejo NM, González-Pardo H, Gonzalez-Lima F, Arias JL. Spatial learning of the water maze: Progression of brain circuits mapped with cytochrome oxidase histochemistry. Neurobiol Learn Mem. 2010;93: 362–371. doi: 10.1016/j.nlm.2009.12.002 19969098

97. Official journal of the European Communities. Legislation. [Internet]. [Office for Official Publications of the European Communities]; Available: https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=OJ:L:2010:276:TOC

98. Benefiel AC, Dong WK, Greenough WT. Mandatory 'Enriched' Housing of Laboratory Animals: The Need for Evidence-based Evaluation. ILAR J. 2005;46: 95–105. doi: 10.1093/ilar.46.2.95 15775019

99. Bayne K. Potential for Unintended Consequences of Environmental Enrihment for Laboratory Animals and Research Results. ILAR J. 2005;46: 129–139. doi: 10.1093/ilar.46.2.129 15775022

Článek vyšel v časopise


2019 Číslo 12
Nejčtenější tento týden