Anksiyete araştırmalarında kullanılan sıçan davranış modelleri

Aslı Aykaç; Kaya Süer; Cahit Taşkıran

doi:10.5472/MMJ.2015.03661.1

-

Year 2015, Volume: 28 Issue: 1, 1 - 7, 02.07.2015

Aslı Aykaç , Kaya Süer Cahit Taşkıran

https://doi.org/10.5472/MMJ.2015.03661.1

Cited By: 1

Abstract

This review focuses on the methods of study that investigated the anxiolytic effects of new drugs with animal models. In a research setting, researchers investigate inquiry and recognition behavior changes of animals with anxiety in response to drug therapy. This forms the basis of a research. Although, “anxious” behaviors of rats do not exactly match the actual human behavior, they are still used as a model of human behavior. Several different stressor agents have been used including electric shocks, tilting the cage, olfactory bulbectomy, elevation of the setup, changing the lighting situation, under water trauma or exposure to predator materials. In these studies, generally the reaction to the stress is tested by observing the changes in the “anxious” behavior, cognitive impairment, fear and decreased social interaction. Frequently used models are; open field test, forced swimming test, social isolation, conflict tests, repeated stress test, tail suspension test, elevated maze tests, single prolonged test and chronical mild stress predator scane test. We explain various rat models and their properties and show how they are used to create anxiety with different stressor agents. Ease and repeatability of these models suggest that they are effective for studying drugs for the prevention and treatment of anxiety

Keywords

Anxiety, Rat behavior, Animal models

References

1. Diagnostic and Statistical Manual of Mental Disorders: DSM-V. Amer Psychiatric Pub Incorporated, 2013.
2. Barnett SA. The rat: a study in behavior. New Jersey: Transaction Publishers, 2007.
3. Belzung C, Misslin R, Vogel E. Anxiogenic effects of methyl- carboline-carboxylate in a light/dark choice situation. Pharmacol Biochem Behav 1987;28:29-33. doi:10.1016/0091- 3057(90)90260-O
4. Montgomery KC. The relation between fear induced by novel stimulation and exploratory behaviour. J Comp Physiol Psychol 1955;48:254-60. doi: 10.1037/h0043788
5. Foa EB, Keane TM, Freidman MJ, Kohen JA, (editors). Effective Treatments for PTSD: Practice Guidelines From the International Society of Traumatic Stress Studies. New York: Guilford Press, 2005.
6. Boissier JR, Simon P, Soubrie P, Airaksinen M, (editors). New approaches to the study of anxiety and anxiolytic drugs in animal: CNS and behavioral pharmacology. New York: Pergamon, 1976.
7. Ohl F. Testing for anxiety. Clin Neurosci Res 2003;3:233-8. doi:10.1016/S1566-2772(03)00084-7
8. Uzbay T. Depresyon Modelleri, PsikofarmakolojininTemelleri ve Deneysel Araştırma Teknikleri. Ankara: Çizgi Tıp Yayınevi, 2004.
9. Pynoos RS, Ritzmann RF, Steinberg, AM, Goenjian A, Prisecaru I. A behavioral animal model of post traumatic stress disorder featuring repeated exposure to situational reminders. Biol Psychiatry 1996;39:129-34. doi:10.1016/0006- 3223(95)00088-7
10. 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;38:539-46. doi:10.1016/0006- 3223(94)00369-E
11. Rau V, De Cola JP, Fanselow MS. Stress-induced enhancement of fear learning: An animal model of post traumatic stress disorder. Neurosci Biobehav Rev 2005;29:1207-23. doi:10.1016/j.neubiorev.2005.04.010
12. Richter LG. Acute and long-term behavioral correlates of underwater trauma: Potential relevance to stress and post stress syndromes. Psychiatry Res 1998;79:73-83. doi:10.1016/ S0165-1781(98)00030-4
13. Kohda K, Harada K, Kato K, et al. Glucocorticoid receptor activation is involved in producing abnormal phenotypes of single prolonged stress rats: A putative post traumatic stress disorder model. Neurosci 2007;148:22-33. doi:10.1016/j. neuroscience.2007.05.041
14. Cohen, H, Joseph Z, Matar M. The relevance of differential response to trauma in an animal model of posttraumatic stress disorder. Bio Psychic 2003;53:463-73. doi:10.1016/S0006- 3223(02)01909-1
15. Rodgers RJ, Dalvi A. Anxiety, defence and the elevated plusmaze. Neurosci Biobehav Rev 2007;21:801-10. doi: 10.1016/ SO149-7634(96)00058-9
16. Prut I, Belzung C. The open field as an a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J of Pharmacol 2003;463:3-33. doi:10.1016/S0014- 2999(03)01272-X
17. Belzung C. Measuring exploratory behavior. In: Crusio WE, Gerlai RT, editors. Handbook of Molecular Genetic Techniques for Brain and Behavior Research: Techniques in the Behavioral and Neural Sciences. Amsterdam: Elsevier, 1999:739-49.
18. Porsolt RD, Bertin A, Blavet N, et al. Behavioral despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol 1978;47:379-91.
19. Lucki I. The forced swimming test as a model for core and component behavioral effects of antidepressant drugs. Behav Pharmacol 1997;8:523-32.
20. Willner P. Animal models as simulations of depression. Trends Pharmacol Sci 1991;12:131-6. doi:10.1016/0165- 6147(91)90529-2
21. Lyons DM. Animal models of anxiety disorders. In: Schatzberg AF, Nemeroff CB, editors. The American Psychiatric Publishing Texbook of Psychoparmacology. 4th edition. Arlington: American Psychiatric Publishing, 2009:153-9.
22. Vogel JR, Beer B, Clody DE. A simple and reliable conflict procedure for testing anti-anxiety agents. Psychopharmacol 1971;21:1-7.
23. Wall PM, Messier C. Methodological and conceptual issues in the use of the elevated plus-maze as a psychological measurement instrument of animal anxiety-like behavior. Neurosci Biobehav Rev 2001;25:275-86. doi:10.1016/S0149- 7634(01)00013-6
24. 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;14:149-67. doi:10.1016/0165-0270(85)90031-7
25. O’Neill MF, Moore NA. Animal models of depression: are there any? Hum Psychopharmacol Clin Exp 2003;18:239-54.
26. Willner P. Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacol 1997;134:319-29. doi: 10.1007/ s002130050456
27. Blanchard RJ, McKittrick CR, Blanchard DC. Animal model of social stress: effects on behavior and brain neuro- chemical systems. Physiol Behav 2001;73:261-71. doi:10.1016/S0031- 9384(01)00449-8
28. Kocahan S, Akıllıoğlu K, Babar Melik E, Melik E. Beyin ve davranışlar üzerine sosyal çevrenin etkileri. İstanbul Tıp Derg 2010;73:108-12.
29. Hellemans KGC, Benge LC, Olmstead MC. Adolescent enrichment partially reverses the social isolation syndrome. Dev Brain Res 2004;150:103-15. doi: 10.1016/j. devbrainres.2004.03.003
30. Cohen H, Zoher J. An animal model of posttraumatic stress disorder: The use of cut-off behavioral criteria. Ann N Y Acad Sci 2004; 1032: 167-78. doi: 10.1196/annals.1314.014
31. Mazor A, Matar MA, Kaplan Z, Kozlovsky N, Zohar J, Cohen H. Gender-related qualitative differences in baseline and poststress anxiety responses are not reflected in the incidence of criterion-based PTSD-like behaviour patterns. Bio Pschy 2007;1:1-14. doi:10.1080/15622970701561383.
32. Kesner Y, Zohar J, Merenlender A, I Gispan, F Shalit, G Yadid. WFS1 gene as a putative biomarker for development of post-traumatic syndrome in an animal model. Mol Psychiatr 2009; 14: 86-94. doi:10.1038/sj.mp.4002109
33. Aykaç A, Aydın B, Cabadak H, Gören M. The change in muscarinic receptor subtypes in different brain regions of rats treated with fluoxetine or propranolol in a model of posttraumatic stress disorder. Behav Brain Res 2012; 232:124-29. doi:10.1016/j.bbr.2012.04.002
34. Nowak G, Szewczyk B, Wieranska JM, et al. Antidepressant like effect of acute and chronic treatment with zinc in forced swim test and olfactory bulbectomy model in rat. Brain Res Bull 2003;61:159-64.
35. Kelly JP, Wrynn AS, Leonard BE. The olfactory bulbectomized rat as a model of depression: an update. Pharmacol Ther 1997;74:299-316. doi:10.1016/S0163-7258(97)00004-1
36. Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacol 1985;85:367-70. doi:1 0.1007/BF00428203
37. Jelen P, Soltysik S, Zagrodzka J. 22-kHz Ultrasonic vocalization in rats as a index of anxiety but fear: behavioral pharmacological modulation of affective state. Behav Brain Res 2003;141:63-72. doi:10.1016/S0166-4328(02)00321-2
38. Brudzynski SM. Pharmacological and behavioral characteristic of 22kHz alarm calls in rats. Neurosci Biobehav Rev 2001;25:611-7. doi:10.1016/S0149-7634(01)00058-6

Anksiyete araştırmalarında kullanılan sıçan davranış modelleri

Year 2015, Volume: 28 Issue: 1, 1 - 7, 02.07.2015

Aslı Aykaç , Kaya Süer Cahit Taşkıran

https://doi.org/10.5472/MMJ.2015.03661.1

Cited By: 1

Abstract

Klinik öncesi çalışmalar kapsamında oluşturulan hayvan modelleri ile yeni ilaçların anksiyolitik etkileri araştırılmaktadır. Bu modellerde en sık kullanılan hayvanlar sıçanlar ve farelerdir. Anksiyete oluşturulan hayvanlarda; çevreyi araştırma ve tanıma davranışlarındaki değişiklikleri inceleyerek, ilaca verilen yanıta bu davranışlardaki değişimlerin saptanması araştırmaların temelini oluşturmaktadır. İnsanlarda görülen anksiyete davranışlarını tam olarak karşılamamakla birlikte hayvan modellerinde sıçanlardaki bu davranışlar modelin esasını oluşturmaktadır. Stres yaratan etken olarak; elektrik şoku, kafeslere eğim verilmesi, olfaktor bulbektomi, ortamın yükseltilmesi, aydınlatmanın değiştirilmesi, sosyal izolasyon, sualtı travmaları, saldırgan hayvanın kendisine ya da saldırgan hayvana ait ipuçlarına (saldırgana ait koku, tüy, idrar vb) maruz bırakma kullanılmaktadır. Oluşturulan strese karşı bu çalışmalarda genellikle aşırı irkilme, bilişsel bozukluklar, gelişmiş korku, düşük sosyal etkileşim gibi anksiyete davranışlarındaki değişimler ölçülmektedir. Sık kullanılan modeller arasında; açık alan, zorunlu yüzme, çatışma testleri, tekrarlayan stres uygulamaları, kuyruktan asma, yükseltilmiş labirentler, sosyal izolasyon, uzun süreli tek bir strese maruz bırakma, kronik hafif stres ve saldırgan ya da saldırgan ile ilgili ipuçlarına maruz bırakma testlerini saymak mümkündür.Bu derlemede, farklı stresörler ile anksiyete oluşturmada kullanılan sıçan modelleri tanımlanmaktadır. Modellerin özellikleri ve kullanım alanları gözden geçirildiğinde; kolay oluşturulabilir ve tekrarlanabilir oluşları, yeni geliştirilmekte olan ilaçların ya da mevcut benzer ilaçların anksiyeteyi önleme ve tedavi edici etkileri daha etkin olarak araştırılmaktadır.

Keywords

Anksiyete, Sıçan davranışları, Hayvan modelleri

References

1. Diagnostic and Statistical Manual of Mental Disorders: DSM-V. Amer Psychiatric Pub Incorporated, 2013.
2. Barnett SA. The rat: a study in behavior. New Jersey: Transaction Publishers, 2007.
3. Belzung C, Misslin R, Vogel E. Anxiogenic effects of methyl- carboline-carboxylate in a light/dark choice situation. Pharmacol Biochem Behav 1987;28:29-33. doi:10.1016/0091- 3057(90)90260-O
4. Montgomery KC. The relation between fear induced by novel stimulation and exploratory behaviour. J Comp Physiol Psychol 1955;48:254-60. doi: 10.1037/h0043788
5. Foa EB, Keane TM, Freidman MJ, Kohen JA, (editors). Effective Treatments for PTSD: Practice Guidelines From the International Society of Traumatic Stress Studies. New York: Guilford Press, 2005.
6. Boissier JR, Simon P, Soubrie P, Airaksinen M, (editors). New approaches to the study of anxiety and anxiolytic drugs in animal: CNS and behavioral pharmacology. New York: Pergamon, 1976.
7. Ohl F. Testing for anxiety. Clin Neurosci Res 2003;3:233-8. doi:10.1016/S1566-2772(03)00084-7
8. Uzbay T. Depresyon Modelleri, PsikofarmakolojininTemelleri ve Deneysel Araştırma Teknikleri. Ankara: Çizgi Tıp Yayınevi, 2004.
9. Pynoos RS, Ritzmann RF, Steinberg, AM, Goenjian A, Prisecaru I. A behavioral animal model of post traumatic stress disorder featuring repeated exposure to situational reminders. Biol Psychiatry 1996;39:129-34. doi:10.1016/0006- 3223(95)00088-7
10. 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;38:539-46. doi:10.1016/0006- 3223(94)00369-E
11. Rau V, De Cola JP, Fanselow MS. Stress-induced enhancement of fear learning: An animal model of post traumatic stress disorder. Neurosci Biobehav Rev 2005;29:1207-23. doi:10.1016/j.neubiorev.2005.04.010
12. Richter LG. Acute and long-term behavioral correlates of underwater trauma: Potential relevance to stress and post stress syndromes. Psychiatry Res 1998;79:73-83. doi:10.1016/ S0165-1781(98)00030-4
13. Kohda K, Harada K, Kato K, et al. Glucocorticoid receptor activation is involved in producing abnormal phenotypes of single prolonged stress rats: A putative post traumatic stress disorder model. Neurosci 2007;148:22-33. doi:10.1016/j. neuroscience.2007.05.041
14. Cohen, H, Joseph Z, Matar M. The relevance of differential response to trauma in an animal model of posttraumatic stress disorder. Bio Psychic 2003;53:463-73. doi:10.1016/S0006- 3223(02)01909-1
15. Rodgers RJ, Dalvi A. Anxiety, defence and the elevated plusmaze. Neurosci Biobehav Rev 2007;21:801-10. doi: 10.1016/ SO149-7634(96)00058-9
16. Prut I, Belzung C. The open field as an a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J of Pharmacol 2003;463:3-33. doi:10.1016/S0014- 2999(03)01272-X
17. Belzung C. Measuring exploratory behavior. In: Crusio WE, Gerlai RT, editors. Handbook of Molecular Genetic Techniques for Brain and Behavior Research: Techniques in the Behavioral and Neural Sciences. Amsterdam: Elsevier, 1999:739-49.
18. Porsolt RD, Bertin A, Blavet N, et al. Behavioral despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol 1978;47:379-91.
19. Lucki I. The forced swimming test as a model for core and component behavioral effects of antidepressant drugs. Behav Pharmacol 1997;8:523-32.
20. Willner P. Animal models as simulations of depression. Trends Pharmacol Sci 1991;12:131-6. doi:10.1016/0165- 6147(91)90529-2
21. Lyons DM. Animal models of anxiety disorders. In: Schatzberg AF, Nemeroff CB, editors. The American Psychiatric Publishing Texbook of Psychoparmacology. 4th edition. Arlington: American Psychiatric Publishing, 2009:153-9.
22. Vogel JR, Beer B, Clody DE. A simple and reliable conflict procedure for testing anti-anxiety agents. Psychopharmacol 1971;21:1-7.
23. Wall PM, Messier C. Methodological and conceptual issues in the use of the elevated plus-maze as a psychological measurement instrument of animal anxiety-like behavior. Neurosci Biobehav Rev 2001;25:275-86. doi:10.1016/S0149- 7634(01)00013-6
24. 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;14:149-67. doi:10.1016/0165-0270(85)90031-7
25. O’Neill MF, Moore NA. Animal models of depression: are there any? Hum Psychopharmacol Clin Exp 2003;18:239-54.
26. Willner P. Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacol 1997;134:319-29. doi: 10.1007/ s002130050456
27. Blanchard RJ, McKittrick CR, Blanchard DC. Animal model of social stress: effects on behavior and brain neuro- chemical systems. Physiol Behav 2001;73:261-71. doi:10.1016/S0031- 9384(01)00449-8
28. Kocahan S, Akıllıoğlu K, Babar Melik E, Melik E. Beyin ve davranışlar üzerine sosyal çevrenin etkileri. İstanbul Tıp Derg 2010;73:108-12.
29. Hellemans KGC, Benge LC, Olmstead MC. Adolescent enrichment partially reverses the social isolation syndrome. Dev Brain Res 2004;150:103-15. doi: 10.1016/j. devbrainres.2004.03.003
30. Cohen H, Zoher J. An animal model of posttraumatic stress disorder: The use of cut-off behavioral criteria. Ann N Y Acad Sci 2004; 1032: 167-78. doi: 10.1196/annals.1314.014
31. Mazor A, Matar MA, Kaplan Z, Kozlovsky N, Zohar J, Cohen H. Gender-related qualitative differences in baseline and poststress anxiety responses are not reflected in the incidence of criterion-based PTSD-like behaviour patterns. Bio Pschy 2007;1:1-14. doi:10.1080/15622970701561383.
32. Kesner Y, Zohar J, Merenlender A, I Gispan, F Shalit, G Yadid. WFS1 gene as a putative biomarker for development of post-traumatic syndrome in an animal model. Mol Psychiatr 2009; 14: 86-94. doi:10.1038/sj.mp.4002109
33. Aykaç A, Aydın B, Cabadak H, Gören M. The change in muscarinic receptor subtypes in different brain regions of rats treated with fluoxetine or propranolol in a model of posttraumatic stress disorder. Behav Brain Res 2012; 232:124-29. doi:10.1016/j.bbr.2012.04.002
34. Nowak G, Szewczyk B, Wieranska JM, et al. Antidepressant like effect of acute and chronic treatment with zinc in forced swim test and olfactory bulbectomy model in rat. Brain Res Bull 2003;61:159-64.
35. Kelly JP, Wrynn AS, Leonard BE. The olfactory bulbectomized rat as a model of depression: an update. Pharmacol Ther 1997;74:299-316. doi:10.1016/S0163-7258(97)00004-1
36. Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacol 1985;85:367-70. doi:1 0.1007/BF00428203
37. Jelen P, Soltysik S, Zagrodzka J. 22-kHz Ultrasonic vocalization in rats as a index of anxiety but fear: behavioral pharmacological modulation of affective state. Behav Brain Res 2003;141:63-72. doi:10.1016/S0166-4328(02)00321-2
38. Brudzynski SM. Pharmacological and behavioral characteristic of 22kHz alarm calls in rats. Neurosci Biobehav Rev 2001;25:611-7. doi:10.1016/S0149-7634(01)00058-6

There are 38 citations in total.

Details

Primary Language	Turkish
Journal Section	Review Makaleler
Authors	Aslı Aykaç Kaya Süer This is me Cahit Taşkıran This is me
Publication Date	July 2, 2015
Published in Issue	Year 2015 Volume: 28 Issue: 1

Cite

APA	Aykaç, A., Süer, K., & Taşkıran, C. (2015). Anksiyete araştırmalarında kullanılan sıçan davranış modelleri. Marmara Medical Journal, 28(1), 1-7. https://doi.org/10.5472/MMJ.2015.03661.1
AMA	Aykaç A, Süer K, Taşkıran C. Anksiyete araştırmalarında kullanılan sıçan davranış modelleri. Marmara Med J. August 2015;28(1):1-7. doi:10.5472/MMJ.2015.03661.1
Chicago	Aykaç, Aslı, Kaya Süer, and Cahit Taşkıran. “Anksiyete araştırmalarında kullanılan sıçan davranış Modelleri”. Marmara Medical Journal 28, no. 1 (August 2015): 1-7. https://doi.org/10.5472/MMJ.2015.03661.1.
EndNote	Aykaç A, Süer K, Taşkıran C (August 1, 2015) Anksiyete araştırmalarında kullanılan sıçan davranış modelleri. Marmara Medical Journal 28 1 1–7.
IEEE	A. Aykaç, K. Süer, and C. Taşkıran, “Anksiyete araştırmalarında kullanılan sıçan davranış modelleri”, Marmara Med J, vol. 28, no. 1, pp. 1–7, 2015, doi: 10.5472/MMJ.2015.03661.1.
ISNAD	Aykaç, Aslı et al. “Anksiyete araştırmalarında kullanılan sıçan davranış Modelleri”. Marmara Medical Journal 28/1 (August 2015), 1-7. https://doi.org/10.5472/MMJ.2015.03661.1.
JAMA	Aykaç A, Süer K, Taşkıran C. Anksiyete araştırmalarında kullanılan sıçan davranış modelleri. Marmara Med J. 2015;28:1–7.
MLA	Aykaç, Aslı et al. “Anksiyete araştırmalarında kullanılan sıçan davranış Modelleri”. Marmara Medical Journal, vol. 28, no. 1, 2015, pp. 1-7, doi:10.5472/MMJ.2015.03661.1.
Vancouver	Aykaç A, Süer K, Taşkıran C. Anksiyete araştırmalarında kullanılan sıçan davranış modelleri. Marmara Med J. 2015;28(1):1-7.

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