DENEY HAYVANLARINDA ANKSİYETE MODELLERİ VE ANKSİYETENİN DEĞERLENDİRİLMESİ

Anksiyete çok farklı duyguları ve semptomları içeren emosyonel bir durumdur. Anksiyetenin 2 tipi vardır. Birincisi; bir olayla ilişkili olarak kişinin kendi kontrolü dışında, belirli bir süre ve şiddette ortaya çıkan ve fizyolojik koşullarda beklenen bir yanıttır, ikincisi ise süresi ya da şiddeti bakımından uygun olmayan ve fizyolojik koşullarda beklenmeyen bir yanıt şeklinde gelişebilir. Anksiyete çalışmalarında kullanılmak üzere deney hayvanlarında anksiyete oluşturmak ve anksiyeteyi veya anksiyete üzerinde çeşili ilaçların önleyici ya da tedavi edici etkisini araştırmak için çeşitli düzenekler ve testler geliştirilmiştir. Bunlar; yeni bir çevre uygulanmasına bağlı anksiyete oluşturma ve değerlendirme yöntemleri olan yükseltilmiş artı labirent ve deriveleri, yükseltilmiş T-labirent, açık alan, merdiven, sosyal izolasyon, yeni çevrenin beslenmeyi baskılaması, sosyal etkileşim, delikli kutu, yabancı bir kokuya maruz bırakma, ödüllendirme-cezalandırma uygulamasına dayanan şartlı zıtlaşma testleri ve cezalandırma uygulamasına dayanan savunmaya yönelik gömme, pasif sakınma, ayak şoku verme, sıcak tabaka, dört tabaka testleridir. Bu derlemede farklı koşullarda anksiyetenin oluşması ya da anksiyete tedavisinde kullanılacak ilaçların değerlendirilmesi amacı ile literatürde kullanılan deney hayvanı anksiyete modelleri ve bu modellerde anksiyeteyi değerlendirme yöntemleri bir arada verilerek, yöntemler arasında bir kıyaslama yapma imkanı sunulması amaçlanmıştır

Anahtar Kelimeler:

Anksiyete, anksiyete modelleri, hayvan davranışı

Anxiety Models in Experimental Animals and Evaluation of Anxiety

Anxiety is an emotional state of different feelings and symptoms. There are 2 types of anxiety: First one is a physiologically expected response, which occurs at a particular time and severity in an uncontrolled manner. Second one is a physiologically unexpected response, which occurs at an inappropriate time and severity. Several tests and equipments have been developed to form anxiety on experimental animals and to make investigations on anxiety or the prognostic or diagnostic effects of anxiety-related drugs. These are the methods for establishing and evaluating anxiety models in a new environment, such as elevated plus maze and derives, elevated T-maze, open field, staircase test, social isolation, novelty supressed feeding, social interaction, holeboard, predatory odor; operant conflict tests for rewardpunishment applications; and experiments with punishment procedures such as defensive burying, passive avoidance, foot shock, hot plate and four plate tests. These review, aimed to give all the methods on the anxiety models used in the literature for establishing anxiety and evaluating the effects of anxiety-related drugs and to compare these methods

Keywords:

Anxiety, anxiety models, animal behavior,

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Eroğlu L. Depresif hastalıkların biyokimyası preklinik çalışmalar (Affektif hastalıklar için deneysel modeller) . Adam E. Depresif Hasta- lıklar 1989, ss 25-34.
Taneli B, Taneli T. Anksiyetenin nöral meka- nizmaları, I. Anksiyete sempozyumu, Dedeman Otel, Nevşehir 5-7 Haziran 1992, ss 1-11 3. Küçük A. Depresyon ve Anksiyete Modeli Oluş- turulan Deney Hayvanlarında Yaş ve Cinsiye- tin Davranış Üzerine Etkisi. Yüksek Lisans Tezi, Erciyes Ün. Sağlık Bilimleri Enstitüsü, Kayseri,Temmuz 2001.
Ohl F. Testing for anxiety. Clinical Neuroscience Research 2003, 3:233-238.
Kayaalp Tıbbi Farmakoloji. Cilt II (9. bas- SO. kı), Feryal Matbaacılık, Ankara 2000, ss 885- 888.
Pellow S, Chopin P, File SE, et al. Validation of open:closed arm entries in an elevated plus maze as a measure of anxiety in the rat. J. Neurosci Methods 1985, 14:149-167.
Moragrega I, Carrasco MC, Vicens P, Redolat R. Spatial learning in male mice with different levels of aggressiveness: effect of housing conditions and nicotine administration. Behavioural Brain Research 2003, 147:1-8.
Carvajal CC, Vercauteren F, Dumant Y, Michalkiewicz M, Quirion R. Aged neuropeptide Y transgenic rats are resistant to acute stress but not maintain spatial and nonspatial learning. Behavioural Brain Research 2004, 153:471-480.
Rimondini R, Agren G, Borjesson S, Sommer W, Heilig M. Persistent behavioural and autonomic super sensitivity to stress following prenatal stress exposure in rats. Behavioural Brain Research 2003, 140: 75-80.
Rodgers RJ, Cao BJ, Dalvi A. Animal models of anxiety, an ethological perspective. Brazilian Journal of Medical and Biological Research 1997, 30:289-304.
Ferguson SA, Cada AM. Spatial learning/ memory and social and nonsocial behaviors in the spontaneously hypertensive, Wistar-Kyoto and Spraque Dawley rat strains. Pharmacology Biochemistry and Behavior 2004, 77:583-594.
Alcalay RN, Giladi E, Pick CG, Gozes I. Intranasal administration of NAP, a neuroprotective peptide, decreases anxiety- like behavior in aging mice in the elevated plus maze. Neuroscience Letters 2003, 1-4.
Ferguson GD, Herschman HR, Storm DR. Reduced anxiety and depression like behavior in synoptatagmin IV (-/-) mice. Neuropharmacology 2004, 47:604-611.
Arendash GW, King DL, Gordon MN, Morgan D, Hatcher JM, et al. Progressive age related behavioral impairments in transgenic mice carrying both mutant amyloid precursor pro- tein and presenilin-1 transgenes. Brain Research 2001, 891:42-53.
Vasconcellos APS, Tabajora AS, Ferrari C, Rocha E, Dalmaz C. Effects of chronic stress on spatial memory in rats is attenuated by lithium treatment. Physiology&Behavior 2003, 79:143-149.
Graeff FG, Viana MB, Tomaz C. The elevated T-maze; a new experimental model of anxiety and memory: effect of diazepam. Brazilian Journal of Medical and Biological Research 1993, 26:67-70.
Strauss CVA, Maisonnette SS, Coimbra NC, Zangrossi H. Effects of N-methyl D-aspartate induced amygdala lesion in rats submitted to the elevated T-maze test of anxiety. Physiology&Behavior 2003, 78:157-163.
Conde C, Costa V, Tomaz C. Effects of emotional reactivity on inhibitory avoidance in the elevated T-maze. Brazilian Journal of Medical and Biological Research 2000, 33:233-236.
Teixeira RC, Zangrossi H, Graeff FG. Behavioral effects of acute and chronic imipramine in the elevated T-maze model of anxiety. Pharmacology Biochemistry and Behavior 2000, 65:571-576.
Poltronieri SC, Zangrossi H, Viana MB. Antipanic-like effect of serotonin reuptake inhibitors in the elevated T-maze. Behavioural Brain Research 2003, 147:185
Carvalho-Netto EF, Nunes-de Souza RL. Use of the elevated T-maze to study anxiety in mice. Behavioural Brain Research 2004, 148:119-132.
Sena LM, Bueno C, Pobbe RLH, et al. The dorsal raphe nucleus exerts opposed control on generalized anxiety and panic-related defensive responses in rats. Behavioural Brain Research 2003, 142:125-133.
Erdoğan F, Gölgeli A, Arman F. The effects of pentylenetetrazole-induced status epilepticus on behavior, emotional memory, and learning in rats. Epilepsy&Behavior 2004, 5:388-393.
Zangrossi H, Graeff FG. Behavioural validation of the elevated T-maze, a new animal model of anxiety. Brain Research Bulletin 1997, 44:1-5.
Jardim MC, Nogueira RL, Graeff FG, Nunes- de-Souza RL. Evaluation of the elevated T- maze as an animal model of anxiety in the mouse. Brain Research Bulletin 1999, 48:407-411.
Sanson LT, Corobrez AP. Long lasting inhibitory avoidance acquisition in rats submitted to the elevated T-maze model of anxiety. Behavioral Brain Research 1999, 101:59-64.
Graeff FG, Netto CF, Zangrossi H. The elevated T-maze as an experimental model of anxiety. Neuroscience and Biobehavioural Reviews 1998, 23:237-246.
Zanoveli JM, Netto CF, Guimaraes FS, Zangrossi H. Systemic and intradorsal periaqueductal gray injections of cholecystokinin sulfated actapeptide (CCK- 8S) induce a panic-like response in rats submitted to the elevated T-maze. Peptides 2004, 25:1935-1941.
Ramos A, Kangerski AL, Basso PF. Evoluation of Lewis and SHR rat strains as a genetic model for the study of anxiety and pain. Behavioral Brain Research 2002, 129: 113-123.
Candland DK. The open field: some comperative data. Annals New York Academy of Sciences 1969, 159:831-851.
Prut I, Belzung C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. European Journal of Pharmacology 2003, 463:3-33.
Phillips KM. Effects of time and administration of ethanol on open field behavior in hamsters. Physiology & Behavior 1982, 29: 785-787.
Lieben CKJ, Oorsouw K, Deutz NEP, Blokland A. Acute tryptophan depletion induced by a gelatin-based mixture impairs object memory but not affective behavior and spatial learning in the rat. Behavioural Brain Research 2004, 151:53-64.
Nowak G, Szewezyk B, Wieranska JM, Branski P, Palucha A, et al. Antidepressant like effects of acute and chronic treatment with zinc in forced swim test and olfactory bulbectomy model in rats. Brain Research Bulletin 2003, 61:159-164.
Medico M, Nicosia A, Grech M, et al. Riluzole restores motor activity in rats with post-traumatic peripheral neuropathy. Neuroscience Letters 2004, 358:37-40.
Shalev U, Kafkafi N. Repeated maternal seperation does not alter sucrose-reinforced and open field behaviors. Pharmacology Biochemistry and Behavior 2002, 73:115
C.S. Hall, Emotional behavior in the rat. III. The relationship between emotionality and ambulatory activity. J Comp Physiol Psychol 1936, 22: 345–352.
Soubrie P. Open field chez le rat:interrelations entre locomotion exploration et emotivite. J. Pharmacol 1971, 2: 457.
Porsolt RD, Anton G, Blavet N, Jalfre M. Behavioural despair in rats, a new model sensitive to antidepressant treatment. European Journal of Pharmacology 1978, 47: 379-391.
Trauth JA, Seidler FJ, Slotkin TA. Persistent and delayed behavioral changes after nicotine treatment in adolescant rats. Brain Research 2000, 880:167-172.
Hidekazu M, Masaya H, Taneo F, Manabu A, Kiyofumi Y, et al. Dissociation of impairment between spatial memory and motor function and emotional behavior in aged rats. Behavioural Brain Research 1998, 91:73-81.
Binder E, Droste SK, Ohl F, Reul JMHM. Regular voluntary exercise reduces anxiety- related behavior and impulsiveness in mice. Behavioral Brain Research 2004, 155: 197- 206.
Frye CA, Petralia SM, Rhodes ME. Estrous cycle and sex differences in performance on anxiety tasks coincide with increases in hippocampal progestrone and 3a, 5a-THP. Pharmacology Biochemistry&Behavior 2000, 67:587-596.
De Angelis L, File SE. Acute and chronic effects of three benzodiazepines in the social interaction anxiety test in mice. Psychopharmacology 1979, 64:127-129.
File SE. The use of social interaction as a method for detecting anxiolytic activity of chlordiazepoxide-like drugs. Journal of Neuroscience Methods 1980, 2: 219-238.
C o m m i s s a r i s R L , F o n t a n a D J . Pharmacological evaluation of potential animal models for the study of antipanic and panicogenic treatment effects. In: Boulton AA, Baker GB, Martin-Iverson MT. Neuromethods: Animal models in Psychiatry II, New Jersey 1991, pp 209.
Porsolt RD, Martin P, Fromage S, Lenegre A, Drieu K. Anti-stress effects of EGb 761 in rodent models. In: Christen Y, Costentin J, Lacour M, Effects of Ginkgo biloba extract (EGb 761) on the central nervous system, 1991, pp 135-145.
Tonissaar M, Philips M, Eller M, Harro J. Sociability trait and serotonin metabolism in the rat social interaction test. Neuroscience Letters 2004, 367:309-312.
Gurtman CG, Morley KC, Li KM, Hunt GE, McGregor IS. Increased anxiety in rats after 3,4-methylenedioxymethamphetamine: association with serotonin depletion. European Journal of Pharmacology 2002, 446:89-96 .
Sanger DJ, Animal models of anxiety and the screening and development of novel anxiolytic drugs. In: Boulton AA, Baker GB, Martin-Iverson MT. Neuromethods: Animal models in Psychiatry II, New Jersey 1991, pp 150-186.
Van Gaalen MM, Steckler T. Behavioural analysis of four mouse strains in an anxiety test battery. Behavioural Brain Research 2000, 115:95-106.
Dielenberg RA, McGregor IS. Defensive behavior in rats towards predatory odors; a review. Neuroscience and Biobehavioural Reviews 2001, 25:597-609.
Blanchard RJ, Yang M, Li C, Gervacio A, Blanchard DC. Cue and context conditioning of defensive behaviors to cat odor stimuli. Neuroscience and Biobehavioural Reviews 2001, 25: 587-595.
Franke H, Kittner H. Morphological alterations of neurons and astrocytes and changes in emotional behavior in pentylenetetrazol-kindled rats. Pharmacology Biochemistry and Behavior 2001, 70:291- 303.
Lang PJ, Davis M, Öhman A. Fear and anxiety, animal models and human cognitive psychophsiology. Journal of Affective Disorders 2000, 61:137-159.
Dielenberg RA, Arnold JC, McGregor IS. Low-dose midazolam attenuates predatory odor avoidance in rats. Pharmacology Biochemistry and Behavior 1999, 62:197- 201.
Sulev K, Anu P, Hendrik L, Vasar E. Cat odor exposure increases the expression of wolframin gene in the amygdaloid area of rat. Neuroscience Letters 2002, 322:116-120.
Schatzberg AF, Nemeroff CB. The American P s y c h i a t r i c P r e s s . T e x t b o o k o f Psychopharmacology, Animal models of anxiety disorders, Koob GF, Heinrichs SC, Britton K, 2 nd ed, section 6,1998, 136-138.
Masserman JH, Yum KS. An analysis of the influence of alcolism experimental neuroses in cats. Psychosom Medical 1946, 8:36-52.
Geller I, Seifler J. The effect of meprobamates, d-amphetamine and promozine an experimentally induced conflict in the rat. Psychopharmacologia 1960, 11:482-491.
Vogel JR, Beer B, Clody DE. A simple and reliable conflict procedure for testing anti- anxiety agents. Psychopharmacologia 1971, 21:1-7.
George FK, Stephen CH, Karen B. Animal models of anxiety disorders. In: Alan FS, C h a r l e s B N , T e x t b o o k o f Psychopharmacalogy (2 nd ed), American Psychiatric Press, 1998, pp 133-141.
Boissier JR, Simon P, Aron C. A new method for the rapid screening of minor tranquilizers in mice. Eur. J. Pharmacol 1968, 4: 145-151.