Using flies, a wall-following (WAFO) assay has been developed to quantify response to anxiety-inducing or anxiety-reducing stimuli or pharmaceuticals. In an enclosed area, Drosophila typically stay close to the walls during spontaneous locomotion, crossing the center of the field infrequently. A reduction in the WAFO score (increased travel away from the walls) is interpreted as a reduction in anxiety, and an increase in WAFO as an increase in anxiety. The assay must be performed on multiple individual flies, since there is a significant amount of variation between individuals under the same conditions.
This model has been supported by experiments using known modulators of anxiety: (1) WAFO is reduced when the flies are fed diazepam (Valium), which acts via the inhibitory neurotransmitter GABA; (2) WAFO is increased in animals carrying loss-of-function mutations in 5-HT1B (serotonin class 1 receptor) or SerT (serotonin transporter, ortholog of human SLC6A4, see OMIM:607834) and is decreased when either gene is overexpressed; (3) WAFO is increased under environmental stress such as heat shock; (4) WAFO is increased under conditions of prolonged social isolation; (5) supporting observations made in a mouse system, WAFO is reduced by loss-of-function mutations in Dh44-R1 (orthologous to CRHR2 and CRHR1, corticotropin releasing hormone receptors); (6) the large increase in WAFO induced by heat shock is ameliorated by diazepam.
This wall-following assay has been used to assess new gene candidates postulated to affect anxiety-related behaviors; see human disease model reports 'anxiety modulator(s), serotonin class 2 receptor(s)' (FBhh0001006), 'anxiety modulator(s), genes affecting actin filament stability' (FBhh0001007), and 'anxiety modulator(s), CCK-like receptors' (FBhh0001008).
[updated Apr. 2019 by FlyBase; FBrf0222196]