Sei sulla pagina 1di 9
and Toxicological Methods 68 (2013) 175 – 183 Contents lists available at ScienceDirect Journal of

Contents lists available at ScienceDirect

Journal of Pharmacological and Toxicological Methods

journal homepage: www.elsevier.com/locate/jpharmtox

journal homepage: www.elsevier.com/locate/jpharmtox Review Animal models of anxiety: A comprehensive review

Review

Animal models of anxiety: A comprehensive review

Vijender Kumar a , Zulqar Ali Bhat a , , Dinesh Kumar b

a Department of Pharmaceutical Sciences, University of Kashmir, Srinagar 190006, India

b Department of Pharmaceutical Sciences, Tshwane University of Technology, Arcadia Campus, Pretoria 0001, South Africa

of Technology, Arcadia Campus, Pretoria 0001, South Africa article info Article history: Received 29 October 2012

article info

Article history:

Received 29 October 2012 Accepted 9 May 2013

Keywords:

Anxiety

Animal model

Conditioned responses

Stress

abstract

Animal models can be used to contribute to understanding the information about molecular mechanisms involved in anxiety and for screening and developing new medications for their treatment that would be impossible in humans. The human studies have established the genetic basis of anxiety and animal studies have been used to attempt to further clarify its genetic determinants. In the eld of anxiety research, animal models can be grouped into two main classes. The rst involves the animal's conditioned responses to stressful and often painful events (e.g. exposure to electric foot shock) and the second includes ethologically based paradigms and involves the animal's spontaneous or natural reactions (e.g. ight, avoidance and freezing) to stress stimuli that do not explicitly involve pain or discomfort (e.g. exposure to a novel highly illuminated test chamber or to a predator). The current review enlightens the various aspects of animal model of anxiety, which may be used for research purpose.

© 2013 Elsevier Inc. All rights reserved.

Contents

1. Introduction

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2. Validity of animal models

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3. Classi cation of animal models of anxiety

 

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4. Models for anxiety

 

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4.1. Elevated plus-maze (Bourin et al., 2007; Pellow, Chopin, File, & Briley, 1985)

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4.2. Apparatus

 

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4.3. Elevated T-maze (Dutt, Dhar, Sharma, & Dutt, 2011; Onusic, Nogueira, Pereira, Flausino Junior, & Viana, 2003)

 

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4.4. Elevated Zero-Maze model (Kulkarni, Singh, & Bishnoi, 2007; Kumar, Jaiswal, Singh, & Bhattacharya, 2000; Shepherd & Grewal, 1994) .

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4.5. Unstable elevated exposed plus maze (Jones, Duxon, & King, 2002)

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4.6. Y-maze model (Monique et al., 1997)

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4.7. Open eld test

 

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4.8. Hole board test .

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4.9. Hole cross test (Takagi, Watanabe, & Saito, 1971)

 

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4.10. Digital hole-board apparatus (Pathak et al., 2011; Takeda, Tsuji, & Matsumiya, 1998)

 

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4.11. Hole-board apparatus

 

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4.12. Social interaction test (File and Pellow 1985, Min et al., 2005)

 

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4.13. Apparatus and procedure

 

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4.14. Acoustic startle response in rats

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4.15. Procedure

 

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4.16. Vogel thirsty rat con ict test

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4.17. Mirrored chamber test (Dutt et al., 2011, Kulkarni S.K. 1996)

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4.18. Light dark test (Crawley, 1981; Hossain et al., 2010)

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4.19. Suok test and modi ed light dark Suok test (Kalueff & Tuohimaa, 2005)

 

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4.20. Suok test (ST) apparatus

 

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4.21. Testing protocol of Suok test (Bourin & Hascoet, 2003; Crawley, 1999; Kalueff & Tuohimaa, 2005)

 

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4.22. Isolation-induced aggression test (Abramov et al., 2004)

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4.23. Locomotor activity (Rabbani, Wright, & Little, 1995)

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Corresponding author at: Department of Pharmaceutical Sciences, University of Kashmir, Srinagar (J & K) 190006, India. Tel.: +91 9419077701. E-mail addresses: vijenderpareek24@yahoo.com (V. Kumar), zabhat2000@gmail.com (Z.A. Bhat), sharmadinesh82@gmail.com , kumard@tut.ac.za (D. Kumar).

1056-8719/$ see front matter © 2013 Elsevier Inc. All rights reserved.

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V. Kumar et al. / Journal of Pharmacological and Toxicological Methods 68 (2013) 175 183

4.24. Forced swimming test (FST)

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4.25. Learned helplessness test in rats (Bhattacharya, 1994; Katz, 1981; Seligman & Beagley, 1975)

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4.26. Muricidal behavior (Bhattacharya, 1994)

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4.27. Geller type con ict test (Dutt et al., 2011; Umezu, 2000)

 

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4.28. Suppression of feeding by novelty (Bhattacharya, Satyam, & Ramanathan, 1999; Dutt et al., 2011)

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4.29. Social separation (Dutt et al., 2011)

 

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4.30. Chick social separation-stress test (Dutt et al., 2011; Sufka, Roach, & Chambliss, 2001)

 

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4.31. Cat odor exposure (Dutt et al., 2011; Johnston & File, 1988)

 

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4.32. Staircase test (Vogel & Vogel, 1997)

 

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4.33. Foot shock induced aggression test (Tedeschi et al., 1959)

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4.34. Foot shock-induced freezing behavior in rats (Dutt et al., 2011; Vogel & Vogel, 1997)

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4.35. Exploratory rearings (Hiller & Zetler, 1996; Oliva, Gonzalez-Trujano, Arrieta, Enciso-Rodrıguez, & Navarrete, 2004; Ugalde et al., 2005)

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4.36. Four plate test in mice .

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5. Anxiogenic agent-using model

 

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5.1.

Antagonism of discrimination stimuli produced by anxiogenic drugs

 

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6. β-Carboline-induced behavioral syndrome in monkeys

 

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7. Limitation of animal models

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8. Conclusion

 

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Acknowledgment

 

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References

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1. Introduction

Anxiety is affecting one-eighth of the total population of the world and has become a very important area of research interest in psycho- pharmacology in the past decade (Rabbani, Sajjadi, & Zarei, 2003). Phys- ical symptoms of anxiety disorders are due to released stress hormones like adrenaline and cortisol, which have an effect on almost every organ in the body. Untreated anxiety disorders can lead to depression which may result in increased blood pressure, heart palpitations, chest pain, rapid breathing or breathlessness, sweating, increased muscle tension or irritability, and decreased intestinal blood ow resulting in nausea or diarrhea. There is often a decreased sex drive. Children with anxiety may also have a fear of being away from the family, a refusal to go to school, a fear of strangers, a fear of falling asleep or have recurrent nightmares ( Jain, Sharma, & Gahalain, 2010 ). Animal models for psychopathology have become an invaluable tool in the analysis of the multitude of causes, genetic, environmental or pharmacological, that can bring about symptoms homologous to those of patients with a speci c disorder ( Shekhar, McCann, & Meaney, 2001 ) ( Table 3 ).

2. Validity of animal models

An important criterion for developing animal models to study psychopathology involves establishing the validity of the model as a true representation of the process being studied. Generally, three types of validity parameters are applied to animal models: face validity, construct validity, and predictive validity (Bourin, Petit-Demouliere, Dhonnchadha, & Hascoet, 2007):

Face validity, where the model is phenotypically similar and implies that the response observed in the animal model should be identical to the behavioral and physiological responses observed in humans. Predictive validity entails that the model should be sensitive to clinically effective pharmacological agents and conversely anxiogenic compounds should elicit opposite effects, while agents that have no effect in the clinic should have no effect in these tests. Construct validity relates to the similarity between the theoretical rationale underlying the animal model and human behavior. It should be noted that the different types of validity can be independent of each other; an animal model can possess predictive and construct validity without possessing face validity. Ideally, an animal model should possess both construct and predictive validity so that it may be used to understand the mechanisms and etiology of the behavioral

and biological factors underlying the disorder that may be similar in animals and humans. The animal models use experimental pre- parations developed in one species for the purposes of studying phenomena occurring in another species and it helps to identify promising treatments for the disorder ( Belzung, 1999; Pathak, Kasture, Bhatt, & Patel, 2011; Raison & Miller, 2003 ). Mice and humans share more than 90% of their genes, and animal models seem to be a useful tool in biomedical sciences, as evidenced by a notable increase in the number of active laboratories working in the eld ( Belzung, 1999; Belzung & Griebel, 2001; Pathak et al., 2011 ). Furthermore, animal models are particularly of help in situ- ations when the impact of stress cannot be studied in humans be- cause of ethical and other like reasons. However, the choice of which biological phenomenon correlates to study is not easy, since problems with animal models of human psychic disorders in- clude: (i) the difference between humans and nonhuman nervous systems; (ii) the dif culty in determining analogous behaviors among species; and (iii) the need of extrapolation of results from animals to humans. Such problems most likely re ect a signi cant difference in etiology and complexity of anxious behaviors. In addi- tion, it is important to know that the data derived from animal models are of value only to the extent that the models are valid, and that the level (severity) of the disorder evoked in animals may not be the level of human disorder, thus the need for a new model ( Pathak et al., 2011 ).

3. Classi cation of animal models of anxiety

Animal models of anxiety can be classi ed as conditioned unconditioned responses ( Table 1 , B ourin et al., 2007 ) and as exteroceptiveinteroceptive stimuli models (Table 2, Divekar, Oswal, Bagul, & Antre, 2011). The rst involves the animal's conditioned re- sponses to stressful and often painful events and the second includes ethologically based paradigms and involves the animal's spontaneous or natural reactions to stress stimuli that do not explicitly involve pain or discomfort (Bourin et al., 2007).

4. Models for anxiety

4.1. Elevated plus-maze ( Bourin et al., 2007; Pellow, Chopin, File, & Briley, 1985