Elevated plus maze

Schematic drawing of the Elevated Plus Maze setup for rats.
An elevated plus maze for mice

The elevated plus maze (EPM) is an animal model of anxiety that usually uses rodents as a screening test for putative anxiolytic or anxiogenic compounds and as a general research tool in neurobiological anxiety research. The model is based on the test animal's aversion to open spaces and tendency to be thigmotaxic (a preference to remain near to, or touching, vertical surfaces). In the EPM, this is expressed as the animal spending more time in the enclosed arms.

Method

The test uses a plus-shaped apparatus with two open and two enclosed arms, each with an open roof, elevated 40–70 cm from the floor. The behavioral model is based on rodents' aversion of open spaces. This aversion leads to the behavior termed thigmotaxis, which involves avoidance of open areas by confining movements to enclosed spaces or to the edges of a bounded space. In the EPM, this translates into the animals limiting their movement to the enclosed arms.[1][2][3][4]

Anxiety reduction is indicated in the plus-maze by an increase in the proportion of time spent in the open arms (time in open arms/total time in open or closed arms), and an increase in the proportion of entries into the open arms (entries into open arms/total entries into open or closed arms). The total number of arm entries and number of closed-arm entries are sometimes used as measures of general activity.[5] The relationship between the EPM and other tests of exploratory activity (open-field and emergence) have been analyzed in two mouse strains.[6]

Controversy

While EPM is the most commonly employed animal behavioral model of anxiety, there are several issues concerning the validity of the model. Classical clinical anxiolytics, such as benzodiazepines (e.g., Valium), do reduce measures of anxiety in EPM. However, more novel compounds, such as 5-HT1A agonists (e.g., Buspar) give mixed results. Selective serotonin reuptake inhibitors and tricyclic antidepressants, which are commonly employed in clinical settings to treat anxiety disorders, also do not lead to a stable anxiolytic effect on EPM.[4] This raises the possibility that EPM is a suitable model for testing GABA-related compounds, such as benzodiazepines or direct GABAA agonists, but not for other drugs. Despite this, the model is commonly employed for screening putative anxiolytics and for general research into the brain mechanisms of anxiety,[7] likely due to the ease of employment and the vast number of studies already in the literature.

Variations

Elevated Zero Maze (EZM)

Mouse on the EZM

The EZM is a circular runway elevated from the floor that consists of alternating open lit area and enclosed dark areas.[8][9] The uninterrupted nature of the runway eliminates the problem of the center area of the EPM. In the EPM test subjects will spend up to 30% of their time in the ambiguous central start area or return to it often, which makes it difficult to evaluate anxiety related behaviour. The central start area is neither open or closed. Test subjects will return to it because they are semi-acclimatized to that area already and know that area is safe.[10]

In untreated rodents EZM showed higher exploration of open areas then in the EPM which suggests that the EPM inhibits exploration because rodents spent time in the central zone of the plus. The EZM is more sensitive to changes then the EPM due to the baseline level in the EZM being lower then the EPM.[8]

Elevated T Maze (ETM)

The ETM has three arms. One arm is closed and is perpendicular to the other two arms which are open forming a T shape. This test is designed to observe anxiety effects and how it affects learning. The rodent is placed on the enclosed arm and allowed to explore. The trial ends when the rodents sets all four paws in on the open arms. Rats are allowed multiple trials until they learn to stay in the open arm for 300 seconds. This is a measurement of inhibitory avoidance.Depending on what the rodents were treated with during the training sessions, they would learn at different rates giving information on how the brain stores memories.[11] This test can be used to assess long term memory. When a rodent has been sufficiently trained, researchers will test the rodent again after a week to observe if the rodent still remembers to stay in the enclosed arm.

See also

External Links

References

  1. ↑ Pellow, S., Chopin, P., File, S.E. and Briley, M. (1985). "Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat". J. Neurosci. Methods 14: 149–67. doi:10.1016/0165-0270(85)90031-7.
  2. ↑ Treit, D., Menard, J. and Royan, C. (1993). "Anxiogenic stimuli in the elevated plus-maze". Pharmacol. Biochem. Behav. 44: 463–469. doi:10.1016/0091-3057(93)90492-c.
  3. ↑ Rodgers, R.J. (1997). "Animal models of anxiety: where next?". Behav. Pharmacol. 8: 477–496. doi:10.1097/00008877-199711000-00003.
  4. 1 2 Carobrez, A.P. and Bertoglio, L.J. (2005). "Ethological and temporal analyses of anxiety-like behavior: the elevated plus-maze model 20 years on". Neurosci. Biobehav. Rev. 29: 1193–1205. doi:10.1016/j.neubiorev.2005.04.017.
  5. ↑ Hogg S.A. (1996). "Review of the validity and variability of the elevated plus-maze as an animal model of anxiety". Pharmacol. Biochem. Behav. 54: 21–30. doi:10.1016/0091-3057(95)02126-4.
  6. ↑ Lalonde, R; Strazielle C (2008). "Relations between open-field, elevated plus-maze, and emergence tests as displayed by C57/BL6J and BALB/c mice". Journal of Neuroscience Methods 171 (1): 48–52. doi:10.1016/j.jneumeth.2008.02.003. PMID 18358538.
  7. ↑ Engin, E. and Treit, D. (2008). "The effects of intra-cerebral drug infusions on animals' unconditioned fear reactions: A systematic review.". Prog. Neuropsychopharmacol. Biol. Psychiatry. doi:10.1016/j.pnpbp.2008.03.020.
  8. 1 2 Braun, Amanda A; Skelton, Matthew R; Vorhees, Charles V; Williams, Michael Y (2011). "Comparison of the elevated plus and elevated zero mazes in treated and untreated male Sprague-Dawley rats: Effects of anxiolytic and anxiogenic agents". Pharmacol Biochem Behav 97 (3): 406-415.
  9. ↑ Campos, Alline C; Fogaca, Manoela V; Aguiar, Daniele C; Guimaraes, Francisco S (2013). "Animal models of anxiety disorders and stress". Revista Brasileira de Psiquiatria 35: 101-111.
  10. ↑ Bailey, KR; Crawley, JN (2009). Methods of Behavior Analysis in Neuroscience (2nd ed.). Boca Raton (FL): CRC Press/Taylor & Francis. Retrieved 13 April 2016.
  11. ↑ Asth, Laila; Rachetti, Vanessa; Gavioli, Elaine C; Andre, Eunice; Lobao-Soares, Bruno (2012). "The elevated T-maze task as an animal model to simultaneously investigate the effects of drugs on long-term memory and anxiety in mice". Brain Research Bulletin 87: 526-533.
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