The Plus-Maze Discriminative Avoidance Task: An Ethical Rodent Model for Concomitant Evaluation of Learning, Memory, Anxiety, Motor Activity and Their Interactions

The elevated plus-maze consists of two open, elevated arms running along a north-south axis and two arms enclosed by walls running east-west. It combines elements of unfamiliarity, openness and elevation (see Chap. 16). Since its introduction by Handley and Mithani (1984) and experimental validation for rats (Pellow et al. 1985) and mice (Lister 1987), it has been most extensively used to asses anxiolytic and anxiogenic effects of drugs in several hundred studies. Standard anxiolytic and anxiogenic drugs increase and decrease, respectively, both the percentage of time that rats (or mice) spend in the open arms and the percentage of entries that they make into the open arms. However, due to its widespread appeal, the elevated plus-maze has also been used to measure levels of spontaneous anxiety behavior (Goto et al. 1993), to investigate anxiety-induced antinociception (Lee and Rodgers 1990; Frussa-Filho et al. 1992; Conceicao et al. 1992; Rodgers et al. 1992) and to evaluate memory. Regarding this latter use, Itoh et al. (1990) proposed that the retesting-induced decrease in the time taken by the animal to move from an open arm to an enclosed arm in the elevated plus-maze could be a measure of memory. This suggestion has been corroborated and extended by others (Frussa-Filho et al. 1991; Graeff et al. 1993; Conceicao et al. 1994). For example, Graeff et al. (1993) showed that the retesting-induced increase in the time taken by the animal to move from an enclosed arm to an open arm could be used as an inhibitory avoidance task to measure memory.