Emotional and Anxiety Assessments in CNS Disorders - Animal Models of Acute Neurological Injuries: Injury and Mechanistic Assessments - page 244

as sudden extreme fear accompanied by autonomic nervous system
arousal (American Psychiatric Association). Another important
concept about anxiety is state vs. trait anxiety. State anxiety is that
observed at any time and the exaggeration is always associated with
a sudden stressor and remits once the stimulus is removed. Trait
anxiety is persistent in an individual, which may have heritable
components.
In order to fi nd a treatment for anxiety, animal behavior models
are required to screen the compounds which have anxiolytic effect.
1960s-1980s could be considered as the behavioral decades for
the research on the preclinical study of anxiety. In this period, some
of the most important anxiety behavioral tests were developed ( 1 ).
The light/dark (LD) box and elevated plus maze (EPM) were
developed in the 1980s to test anxiety-related behavior ( 2 ). The open
fi eld, which was originally used to score “emotionality” in rats, was
adopted as an anxiety test ( 3 ). The social interaction test, focusing
on ethologically relevant concepts, was developed in 1978 ( 4 ).

1.1. Elevated Plus
Maze

The EPM is the most widely used task to study emotional behavior,
and in particular anxiety. It has an extremely high predictive validity,
and therefore it is useful to test the effi cacy of novel drugs for anxiety.
The rationale of this test is that rodent has intrinsic tendency to
explore novel environments but has aversion to open and high
location. This aversion leads to the thigmotaxis, which is defi ned as
avoidance of open areas by confi ning movements to enclosed spaces
or to the edges of enclosed space. Administration of anxiolytic com-
pound, such as benzodiazepines, increases exploration of the open
arm and visit times to open arm.

The size of the EPM apparatus has slight difference for rat and
mice. The size of the EPM for rat consists of two sets of opposing
arms with a matte black acrylic surface. Two open arms without
walls and two closed arms enclosed by 30-cm-high walls are
extended 50 cm from central. Each arm is 10 cm wide. The arms
of the EPM for mice are 30 cm long and 5 cm wide (Columbus
Instruments). Closed arms are enclosed by 15.25-cm-high walls.
Each arm is painted matte black. Each arm of the maze is attached
to metal, plastic, or wood legs, so it is elevated 50 cm (rat) or 40 cm
(mice) off a base that it is on. Some labs installed 3-5-mm-high railing
on the open arm of the EPM to increase open arm exploration.

1.1.1. Materials
and Equipment

Bring rodents, which are in individual temporary transport cage, to
the experiment room 1 h prior to testing. The illumination in the
experiment room should be consistent during the behavioral test.
The animals are very sensitive to the change of illumination, which
could result in biased results. High level of illumination would
restrict the natural exploratory tendency of rodents. One particular
behavior room for EPM is illuminated with six 32-W fl uorescent

1.1.2. Methods