Evaluation of the effects of L-Theanine on neurobehavior in an adult male Sprague-Dawley Rat Model of PTSD
DOI:
https://doi.org/10.14719/pst.2019.6.3.564Keywords:
PTSD, Neurobehavior, L-Theanine, Green Tea, RatAbstract
Post-traumatic stress disorder (PTSD) continues to be one of the most common mental health disorders in the United States and may occur in response to traumatic experiences. Currently, there are no interventions that prevent the development of PTSD. L-Theanine (L-Th), a major compound in green tea has been found to decrease anxiety and prevent memory impairment and may have potential effects in the prevention of PTSD. Sixty rats were divided into six experimental groups: control vehicle, control L-Th, control naïve, PTSD vehicle, PTSD Pre-L-Th (prophylactic), PTSD Post-L-Th (non-prophylactic). PTSD was induced by a 3-day restraint/tail shock stress model. The effects of L-Th on neurobehavior were evaluated by Elevated Plus-Maze (EPM), Morris Water Maze (MWM), and Forced Swim Test (FST). Our study found that the total food intake weight of PTSD Pre-L-Th (prophylactic) rats were significantly increased compared to that of PTSD vehicle rats (p = .04). Administration of L-Th 24 hours before the initial PTSD event or for 10 days following the last PTSD stress event did not statistically improve mean open arm exploration on the EPM, spatial memory, and learning in the MWM or behavioral despair measured by the FST (p > 0.05). Although the 3-day restraint/tail shock stress model caused stress in the rodents, it did not produce reported PTSD-like anxiety and depression or spatial memory loss. The effect of Pre-L-Th or Post-L-Th treatment, on the neurobehavioral functions could not be effectively evaluated. However, this study provides a foundation for future studies to try different rodent PTSD models to induce PTSD-like neurobehavioral impairments to explore dosage, frequency, as well as the duration of L-Th administration before and/or after the post-traumatic event. The 3-day restraint/tail shock stress model caused stress in the rodents, Pre-L-Theanine treatment preconditioned the PTSD rats to endure stress.
Downloads
References
2. Kilpatrick DG, Resnick HS, Milanak ME, Miller MW, Keyes KM, Friedman MJ. National estimates of exposure to traumatic events and PTSD prevalence using DSM-IV and DSM-5 criteria. J Trauma Stress. 2013; 26(5):537-47. https://doi.org/10.1002/jts.21848
3. Eber S, Barth S, Kang H, Mahan C, Dursa E, Schneiderman A. The National Health Study for a New Generation of United States Veterans: methods for a large-scale study on the health of recent veterans. Mil Med. 2013; 178(9):966-9. https://doi.org/10.7205/MILMED-D-13-00175
4. Sareen J. Posttraumatic stress disorder in adults: impact, comorbidity, risk factors, and treatment. Can J Psychiatry. 2014; 59(9):460-7. https://doi.org/10.1177/070674371405900902
5. Marmar CR, Schlenger W, Henn-Haase C, Qian M, Purchia E, Li M, et al. Course of Posttraumatic Stress Disorder 40 Years After the Vietnam War: Findings From the National Vietnam Veterans Longitudinal Study. JAMA Psychiatry 2015; 72(9):875-81. https://doi.org/10.1001/jamapsychiatry.2015.0803
6. Koenen KC, Ratanatharathorn A, Ng L, McLaughlin KA, Bromet EJ, Stein DJ, et al. Posttraumatic stress disorder in the World Mental Health Surveys. Psychol Med. 2017; 47(13):2260-74. https://doi.org/10.1017/S0033291717000708
7. Stein MB, McQuaid JR, Pedrelli P, Lenox R, McCahill ME. Posttraumatic stress disorder in the primary care medical setting. Gen Hosp Psychiatry. 2000; 22(4):261-9. https://doi.org/10.1016/S0163-8343(00)00080-3
8. Association AP. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. 5 ed. Washington, D.C.2013.
9. Roca V, Freeman TW. Complaints of impaired memory in veterans with PTSD. Am J Psychiatry. 2001; 158(10):1738-9. https://doi.org/10.1176/appi.ajp.158.10.1738-a
10. Brewin CR, Kleiner JS, Vasterling JJ, Field AP. Memory for emotionally neutral information in posttraumatic stress disorder: A meta-analytic investigation. J Abnorm Psychol. 2007; 116(3):448-63. https://doi.org/10.1037/0021-843X.116.3.448
11. Scott JC, Matt GE, Wrocklage KM, Crnich C, Jordan J, Southwick SM, et al. A quantitative meta-analysis of neurocognitive functioning in posttraumatic stress disorder. Psychol Bull. 2015; 141(1):105-40. https://doi.org/10.1037/a0038039
12. Brailey K, Vasterling JJ. Neuropsychological findings in adults with PTSD. In: Vasterling JJ, Brailey K, editors. Neuropsychology of PTSD: Biological, cognitive, and clinical perspectives. Vasterling JJ, Brailey K, editors. New York: Guilford Press; 2005.
13. Bremner JD, Randall P, Scott TM, Bronen RA, Seibyl JP, Southwick SM, et al. MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. Am J Psychiatry. 1995; 152(7):973-81. https://doi.org/10.1176/ajp.152.7.973
14. Liberzon I, Sripada CS. The functional neuroanatomy of PTSD: a critical review. Prog Brain Res. 2008; 167:151-69. https://doi.org/10.1016/S0079-6123(07)67011-3
15. Morey RA, Gold AL, LaBar KS, Beall SK, Brown VM, Haswell CC, et al. Amygdala volume changes in posttraumatic stress disorder in a large case-controlled veterans group. Arch Gen Psychiatry. 2012; 69(11):1169-78. https://doi.org/10.1001/archgenpsychiatry.2012.50
16. Etkin A, Wager TD. Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. Am J Psychiatry. 2007; 164(10):1476-88. https://doi.org/10.1176/appi.ajp.2007.07030504
17. Hedges DW, Woon FL. Premorbid brain volume estimates and reduced total brain volume in adults exposed to trauma with or without posttraumatic stress disorder: a meta-analysis. Cogn Behav Neurol. 2010; 23(2):124-9. https://doi.org/10.1097/WNN.0b013e3181e1cbe1
18. Karl A, Schaefer M, Malta LS, Dorfel D, Rohleder N, Werner A. A meta-analysis of structural brain abnormalities in PTSD. Neurosci Biobehav Rev. 2006; 30(7):1004-31. https://doi.org/10.1016/j.neubiorev.2006.03.004
19. Kitayama N, Vaccarino V, Kutner M, Weiss P, Bremner JD. Magnetic resonance imaging (MRI) measurement of hippocampal volume in posttraumatic stress disorder: a meta-analysis. J Affect Disord. 2005; 88(1):79-86. https://doi.org/10.1016/j.jad.2005.05.014
20. Kuhn S, Gallinat J. Gray matter correlates of posttraumatic stress disorder: a quantitative meta-analysis. Biol Psychiatry. 2013; 73(1):70-4. https://doi.org/10.1016/j.biopsych.2012.06.029
21. Scott JC, Harb G, Brownlow JA, Greene J, Gur RC, Ross RJ. Verbal memory functioning moderates psychotherapy treatment response for PTSD-Related nightmares. Behav Res Ther. 2017; 91:24-32. https://doi.org/10.1016/j.brat.2017.01.004
22. Solomon Z, Shklar R, Mikulincer M. Frontline treatment of combat stress reaction: a 20-year longitudinal evaluation study. Am J Psychiatry. 2005; 162(12):2309-14. https://doi.org/10.1176/appi.ajp.162.12.2309
23. Rudy JW, Huff NC, Matus-Amat P. Understanding contextual fear conditioning: insights from a two-process model. Neurosci Biobehav Rev. 2004; 28(7):675-85. https://doi.org/10.1016/j.neubiorev.2004.09.004
24. Dielenberg RA, McGregor IS. Defensive behavior in rats towards predatory odors: a review. Neurosci Biobehav Rev. 2001; 25(7-8):597-609. https://doi.org/10.1016/S0149-7634(01)00044-6
25. Manion ST, Gamble EH, Li H. Prazosin administered prior to inescapable stressor blocks subsequent exaggeration of acoustic startle response in rats. Pharmacol Biochem Behav. 2007; 86(3):559-65. https://doi.org/10.1016/j.pbb.2007.01.019
26. Takahashi T, Morinobu S, Iwamoto Y, Yamawaki S. Effect of paroxetine on enhanced contextual fear induced by single prolonged stress in rats. Psychopharmacology (Berl) 2006; 189(2):165-73. https://doi.org/10.1007/s00213-006-0545-6
27. Goswami S, Samuel S, Sierra OR, Cascardi M, Pare D. A rat model of post-traumatic stress disorder reproduces the hippocampal deficits seen in the human syndrome. Front Behav Neurosci. 2012; 6:26. https://doi.org/10.3389/fnbeh.2012.00026
28. Woodson JC, Macintosh D, Fleshner M, Diamond DM. Emotion-induced amnesia in rats: working memory-specific impairment, corticosterone-memory correlation, and fear versus arousal effects on memory. Learn Mem. 2003; 10(5):326-36. https://doi.org/10.1101/lm.62903
29. Sakato Y. The chemical constituents of tea: III. A new amide theanine. Nippon Nogeikagaku Kaishi. 1949; 23:262-7.
30. Gomez-Ramirez M, Higgins BA, Rycroft JA, Owen GN, Mahoney J, Shpaner M, et al. The deployment of intersensory selective attention: a high-density electrical mapping study of the effects of theanine. Clin Neuropharmacol. 2007; 30(1):25-38. https://doi.org/10.1097/01.WNF.0000240940.13876.17
31. Nathan PJ, Lu K, Gray M, Oliver C. The neuropharmacology of L-theanine(N-ethyl-L-glutamine): a possible neuroprotective and cognitive enhancing agent. J Herb Pharmacother. 2006; 6(2):21-30. https://doi.org/10.1080/J157v06n02_02
32. Ceremuga TE, Martinson S, Washington J, Revels R, Wojcicki J, Crawford D, et al. Effects of L-theanine on posttraumatic stress disorder induced changes in rat brain gene expression. Scientific World Journal 2014; 2014:419032. https://doi.org/10.1155/2014/419032
33. Egashira N, Ishigami N, Pu F, Mishima K, Iwasaki K, Orito K, et al. Theanine prevents memory impairment induced by repeated cerebral ischemia in rats. Phytother Res. 2008; 22(1):65-8. https://doi.org/10.1002/ptr.2261
34. Cho HS, Kim S, Lee SY, Park JA, Kim SJ, Chun HS. Protective effect of the green tea component, L-theanine on environmental toxins-induced neuronal cell death. Neurotoxicology 2008; 29(4):656-62. https://doi.org/10.1016/j.neuro.2008.03.004
35. Tian X, Sun L, Gou L, Ling X, Feng Y, Wang L, et al. Protective effect of l-theanine on chronic restraint stress-induced cognitive impairments in mice. Brain Res. 2013; 1503:24-32. https://doi.org/10.1016/j.brainres.2013.01.048
36. Valdivieso DA, Baughan TG, 2nd, Canavati UM, Rey AM, Trotter CL, Burrell DR, et al. Effects of pregabalin on neurobehavior in an adult male rat model of PTSD. PLoS One. 2018; 13(12):e0209494. https://doi.org/10.1371/journal.pone.0209494
37. Servatius RJ, Ottenweller JE, Natelson BH. Delayed startle sensitization distinguishes rats exposed to one or three stress sessions: further evidence toward an animal model of PTSD. Biol Psychiatry. 1995; 38(8):539-46. https://doi.org/10.1016/0006-3223(94)00369-E
38. Pellow S, Chopin P, File SE, Briley M. Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods. 1985; 14(3):149-67.
39. Morris R. Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods. 1984; 11(1):47-60.
40. Jeong DU, Lee J, Chang WS, Chang JW. Identifying the appropriate time for deep brain stimulation to achieve spatial memory improvement on the Morris water maze. BMC Neurosci. 2017; 18(1):29. https://doi.org/10.1016/0165-0270(85)90031-7
41. D'Hooge R, De Deyn PP. Applications of the Morris water maze in the study of learning and memory. Brain Res Brain Res Rev. 2001; 36(1):60-90. https://doi.org/10.1016/S0165-0173(01)00067-4
42. Wenk GL. Assessment of spatial memory using the radial arm maze and Morris water maze. Curr Protoc Neurosci. 2004; Chapter 8: Unit 8 5A. https://doi.org/10.1002/0471142301.ns0805as26
43. Castagne V, Moser P, Roux S, Porsolt RD. Rodent models of depression: forced swim and tail suspension behavioral despair tests in rats and mice. Curr Protoc Neurosci. 2011; Chapter 8: Unit 8 10A. https://doi.org/10.1002/0471142301.ns0810as55
44. Pek J, Flora DB. Reporting effect sizes in original psychological research: A discussion and tutorial. Psychol Methods. 2018; 23(2):208-25. https://doi.org/10.1037/met0000126
45. Cohen J. Statistical power analysis for the behavioral sciences. 2nd ed. Hillsdale, N.J.: L. Erlbaum Associates: 1988. p.567.
46. Schoner J, Heinz A, Endres M, Gertz K, Kronenberg G. Post-traumatic stress disorder and beyond: an overview of rodent stress models. J Cell Mol Med. 2017; 21(10):2248-56. https://doi.org/10.1111/jcmm.13161
47. Barone FC, Barton ME, White RF, Legos JJ, Kikkawa H, Shimamura M, et al. Inhibition of phosphodiesterase type 4 decreases stress-induced defecation in rats and mice. Pharmacology. 2008; 81(1):11-7. https://doi.org/10.1159/000107662
48. Goswami S, Rodriguez-Sierra O, Cascardi M, Pare D. Animal models of post-traumatic stress disorder: face validity. Front Neurosci. 2013; 7:89. https://doi.org/10.3389/fnins.2013.00089
49. Yokogoshi H, Kobayashi M, Mochizuki M, Terashima T. Effect of theanine, r-glutamylethylamide, on brain monoamines and striatal dopamine release in conscious rats. Neurochem Res. 1998; 23(5):667-73. https://doi.org/10.1023/A:1022490806093
50. Unno T, Suzuki Y, Kakuda T, Hayakawa T, Tsuge H. Metabolism of theanine, gamma-glutamylethylamide, in rats. J Agric Food Chem. 1999; 47(4):1593-6. https://doi.org/10.1021/jf981113t
51. van der Pijl P, Chen L, Mulder TPJ. Human disposition of L-theanine in tea or aqueous solution. Journal of Functional Foods. 2010; 2(4):239-44. https://doi.org/10.1016/j.jff.2010.08.001
52. Kimura K, Ozeki M, Juneja LR, Ohira H. L-Theanine reduces psychological and physiological stress responses. Biol Psychol. 2007; 74(1):39-45. https://doi.org/10.1016/j.biopsycho.2006.06.006
53. Yoto A, Motoki M, Murao S, Yokogoshi H. Effects of L-theanine or caffeine intake on changes in blood pressure under physical and psychological stresses. J Physiol Anthropol. 2012; 31:28. https://doi.org/10.1186/1880-6805-31-28
54. Shacham S. A shortened version of the Profile of Mood States. J Pers Assess. 1983; 47(3):305-6. https://doi.org/10.1207/s15327752jpa4703_14
55. Shoji H, Mizoguchi K. Acute and repeated stress differentially regulates behavioral, endocrine, neural parameters relevant to emotional and stress response in young and aged rats. Behav Brain Res. 2010; 211(2):169-77. https://doi.org/10.1016/j.bbr.2010.03.025
56. Ritov G, Boltyansky B, Richter-Levin G. A novel approach to PTSD modeling in rats reveals alternating patterns of limbic activity in different types of stress reaction. Mol Psychiatry. 2016; 21(5):630-41. https://doi.org/10.1038/mp.2015.169
57. Park SK, Jung IC, Lee WK, Lee YS, Park HK, Go HJ, et al. A combination of green tea extract and l-theanine improves memory and attention in subjects with mild cognitive impairment: a double-blind placebo-controlled study. J Med Food. 2011; 14(4):334-43. https://doi.org/10.1089/jmf.2009.1374
58. Deslauriers J, Toth M, Der-Avakian A, Risbrough VB. Current Status of Animal Models of Posttraumatic Stress Disorder: Behavioral and Biological Phenotypes, and Future Challenges in Improving Translation. Biol Psychiatry. 2018; 83(10):895-907. https://doi.org/10.1016/j.biopsych.2017.11.019
59. Richter-Levin G. Acute and long-term behavioral correlates of underwater trauma--potential relevance to stress and post-stress syndromes. Psychiatry Res. 1998; 79(1):73-83. https://doi.org/10.1016/S0165-1781(98)00030-4
60. Wang J, Akirav I, Richter-Levin G. Short-term behavioral and electrophysiological consequences of underwater trauma. Physiol Behav. 2000; 70(3-4):327-32. https://doi.org/10.1016/S0031-9384(00)00274-2
61. Seligman ME. Learned helplessness. Annu Rev Med. 1972; 23:407-12. https://doi.org/10.1146/annurev.me.23.020172.002203
62. Vollmayr B, Gass P. Learned helplessness: unique features and translational value of a cognitive depression model. Cell Tissue Res. 2013; 354(1):171-8. https://doi.org/10.1007/s00441-013-1654-2
63. Van Dijken HH, Van der Heyden JA, Mos J, Tilders FJ. Inescapable footshocks induce progressive and long-lasting behavioural changes in male rats. Physiol Behav. 1992; 51(4):787-94. https://doi.org/10.1016/0031-9384(92)90117-K
64. Valerio dos Santos C, Gehm T, Hunziker MH. Learned helplessness in the rat: effect of response topography in a within-subject design. Behav Processes. 2011; 86(2):178-83. https://doi.org/10.1016/j.beproc.2010.11.005
Downloads
Published
How to Cite
Issue
Section
License
Copyright and Licence details of published articles
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
Open Access Policy
Plant Science Today is an open access journal. There is no registration required to read any article. All published articles are distributed under the terms of the Creative Commons Attribution License (CC Attribution 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited (https://creativecommons.org/licenses/by/4.0/). Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).