Review Article

Advances in Zebrafish as a Comprehensive Model of Mental Disorders

Table 1

Different behavioral analysis tests of zebrafish in mental disorders.

CategoryBehavior testsSchematic diagram of the devicesMain operating principlesRef.

Behavioral analysis of basic motor and sensory functionsSwimming testThe device contains a pitometer and pressurization. Zebrafish are individually placed into the lane, producing spontaneous movement due to the zebrafish's congenital upstream swimming characteristics. Tested zebrafish will produce spontaneous swimming when the water speed reaches 12 cm/s.[46]
Optokinetic response (OKR)The arena covered by grating stimuli covered most of the zebrafish larvae's visual field. OKR at different stimulus positions, related behavioral performance to photoreceptor densities in the retina.[47]
Stress responseVideo is captured from above 8 swim warehouses. Solenoids piston under the arena.[48, 49]
Visual conditioned/ unconditioned stimulusVideo is captured from above the arena. A single zebrafish is placed in the arena, LCD screen for visually conditioned stimulus beneath the fish tank. Electric shock for unconditioned stimulus. IR LEDs are used to help capture zebrafish traces.[50]

Depression-/anxiety-like behaviorNovel tank test (NTT)The novel tank consists of two arenas. One baseline in the center of the tank divides it into upper and lower arenas. Video picks up fish tracks from the largest side of the tank.[51]
Shoaling testThe video is captured from above the arena. Ten zebrafish were involved in each experiment. Depression-/anxiety-like zebrafish will be reluctant to create closer fish distances.[52]
Light/dark tank testThe video is captured from above the arena. The tank is evenly divided into two arenas. One part of the tank is black and opaque, with a partition in the middle and a 2 cm height leaking from the bottom for the zebrafish to pass through.[53]
Acoustic startle responseThe video is captured from above the arena, video connects to computer for data analysis directly. Zebrafish were put in per hole of a 96-well plate. After acoustic stimulation, the tail of the juvenile fish appears to bend, showing a curved tall.[54]
Video-tracking ExperimentThe video is captured behaviors from above the arena, video connects to computer for data analysis directly. Zebrafish were put in per hole of a 6-well plate. These behaviors include edge and downward movement, speed, movement distance, resting frequency, resting average time, swimming speed, turning angle, and distance between zebrafish.[45]
Novel object approach testThe arena is divided into three sections (inner, transition, and thigmotaxis); there is a Lego man (novel object) put in the inner. Zebrafish were individually placed into the experimental arena.[55]

Behavioral analysis of learning and memorySpatial learning testOne of the stimulus tanks (black areas) contained five conspecific stimulus fish and was not accessible to the experimental fish. The purple areas represent the target zone that is proximal to the location of the stimulus. The yellow areas represent the proximity zones which correspond to the target zone but are adjacent to stimulus tanks without the stimulus.[56, 57]
-plus testThe T-maze is divided into three parts with a 5 cm water depth: (1) “s” area: start arm; (2) “r” area: right area; (3) “w” area: wrong area.[58]
-plus mazeThe -maze is divided into three arms, each arm with 7 cm lane and 1 L aquarium water.[59]
Plus maze3D and 2D drawings of the plus maze. Maze is divided into five parts, d: deep arm; s: shallow arm; c: center zone, which includes intersection and ramps.[60]
Avoidance conditioningAvoidance conditions including light shock and electric shock. Zebrafish would change direction after a conditioned stimulus.[61, 62]

Social behavior analysisSocial interaction testThe tank is divided into three regions: nonsocial, social area, and zebrafish room. When the test starts, remove the opaque wall. Determine the frequency and duration of zebrafish activity in two areas.[58]
Mirror biting testThe tank is the same size as NTT but has a tilted mirror on one side of the vertical plane.[43, 54, 63]
Shoaling testThe video is captured from above the arena. Ten zebrafish were involved in each experiment. This test can determine the distance between zebrafish and swimming speed.[44]
Predator avoidance testThe tank is the same size as NTT but has a predator in one space of the vertical plane.[63]
Social preference testThe tank is divided into five regions. (a) e: social stimulus chamber; b, c, d: tested fish chamber; b, d: area of social preference; c: area of no social preference[64]
Cluster analysisThe swarming score at each time point was calculated every 30 s to determine zebrafish dispersion. The formula is to divide the maximum number of zebrafish in a position of the tank by the number of segments occupied.[65]
Conditioned place preference (CPP)Device can capture preference changes that reflect the effect of giving drug rewards to zebrafish. The tank is divided into two parts, containing three objects of visual cues, and the tank has a perforated wall in the center that allows the zebrafish to traverse freely.[66, 67]