Elevated plus maze

The elevated plus maze (EPM) is a test measuring anxiety in laboratory animals that usually uses rodents as a screening test for putative anxiolytic or anxiogenic compounds and as a general research tool in neurobiological anxiety research such as PTSD and TBI. The model is based on the test animal's aversion to open spaces and tendency to be thigmotaxic. In the EPM, this anxiety is expressed by the animal spending more time in the enclosed arms.

The test uses an elevated, plus-shaped (+) apparatus with two open and two enclosed arms. The behavioral model is based on the general aversion of rodents to open spaces. This aversion leads to the behavior termed thigmotaxis, a preference for remaining in enclosed spaces or close to the edges of a bounded space. In the EPM, this translates into the animals limiting their movement to the enclosed arms.

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. The relationship between the EPM and other tests of exploratory activity (open-field and emergence) have been analyzed in two mouse strains.

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-HT_1A 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. This raises the possibility that EPM is a suitable model for testing GABA-related compounds, such as benzodiazepines or direct GABA_A 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, likely due to the ease of employment and the vast number of studies already in the literature.

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