Use of the elevated plus maze in the search for novel anxiolytic agents.

The elevated plus maze test is a rodent model of anxiety that is used extensively in the discovery of novel anxiolytic agents and to investigate the psychological and neurochemical basis of anxiety. The model is based on Montgomery's 1 observation that rats spent less time exploring the 'open' arms of a novel 'Y'-shaped elevated maze than an enclosed arm. The elevated plus maze used today 2 is in the shape of a cross or plus with two elevated 'closed' arms running along a north-south axis and two elevated 'open' arms running east-west (Fig. la). The test has widespread appeal because: (1) it is quick and simple; (2) the equipment is inexpensive; and (3) in some laboratories the test is able to detect putative anxiolytics, such as CCK B receptor antagonists 3, which lack robust effects in 'classical' animal models of anxiety, i.e. those based on aversive conditioning (Box 1, Box 2). However, the predictive value of the test remains unclear; although anxiolytics, such as the benzodiazepine receptor agonist chlordiazepoxide, produce reliable and reproducible effects, other anxiolytics, such as the partial 5-HT1A receptor agonists 2, do not. This suggests that the use of the elevated plus maze as a model of anxiety has some limitations.