A Novel Behavioral Test Battery to Assess Global Drug Effects Using the Zebrafish

Abstract

The zebrafish (Danio rerio) has been at the forefront of neurobiological research and is steadily gaining favor as a model for behavioral applications. The ease of handling, high yield of progeny, and efficient mode of drug delivery make this species a particularly useful model for behavior. Here, we append to the growing body of literature on zebrafish behavior by introducing a novel behavioral battery of tests aimed at identifying drug induced alterations in social and motoric behaviors. In a series of experiments, zebrafish were exposed to MK-801 (0, 2 µM, 20 µM), SFK 38393 (0, 10 µM, 100 µM), and ethanol (0, 0.5%, 1.0%) for one hour and overt locomotor behaviors were scored. Following a one-hour treatment exposure, circling behavior (a thigmotaxic display typical of dysregulated glutamate function) was scored from videotape at specific time points over a 37-minute session. In a separate experiment the zebrafish's natural tendency to shoal (social display) was analyzed using a novel open-field paradigm that examined fish distribution over quadrants. Most notably, MK-801 (20 µM) significantly increased circling behavior compared to controls. However, shoaling displays were disrupted when zebrafish were exposed to both MK-801 and SKF 38393 (20 µM and 100 µM respectively). Our results, in part, complement existing knowledge about zebrafish behavior following acute drug exposure. Additionally, our novel approach to assessing shoaling behavior, reported here, introduces an alternative view of social/group behavior in the zebrafish that is sensitive to both NMDA and dopaminergic manipulation.

The Behavioral and Pharmacological Actions of NMDA Receptor Antagonism are Conserved in Zebrafish Larvae

“…3 and Gilmour et al, 2009). The EC 50 of the locomotor response to MK-801 in zebrafish larvae is 10 uM, a value that is consistent with the EC 50 of MK-801-evoked behaviors previously described in adult zebrafish (Echevarria et al, 2008;Swain et al, 2004) and rodents (Gilmour et al, 2009). Interestingly, the locomotor actions of MK-801 are dose-dependent and biphasic in both rodents and fish; low concentrations are stimulatory while high concentrations of the drug are are sedating.…”

“…There is compelling evidence that the behavioral, locomotor and cognitive actions of MK-801 are retained in adult zebrafish since the drug disrupts shoaling behavior (Echevarria, Hammack, Pratt, & Hosemann, 2008), increases circling and swimming behavior and decreases performance in conditioned place preference experiments (Swain, Sigstad, & Scalzo, 2004).…”

Does Acute Alcohol Exposure Modulate Aggressive Behaviors in the Zebrafish (Danio rerio), or is the Bark Worse than the Bite?

“…It has been reported that acute alcohol exposure (0.25%, 0.5%, and 1.0% concentrations) disrupts shoaling behavior (Dlugos & Rabin, 2003;Gerlai, 2003;Gerlai et al, 2000). Previous research from our laboratory did not show shoaling disruption with acute exposure to a 1.0% concentration (Echevarria, Hammack, Pratt, & Hosemann, 2008a). In our laboratory, disrupted shoaling was most evident when followed by exposure to 0.5% and 2.0% ethanol concentrations.…”

PIT‐tagging Italian spined loach (Cobitis bilineata): Methodology, survival and behavioural effects

“…This metric measures the motivation and capability of the fish to move, often framed as boldness, activity and/or exploratory tendencies of the fish (Gould et al ., 2009; Perals et al ., 2017). It seems reasonable to think that any severe tagging effects on the fish's physiology would be detected by the test, as for effects of chemical compounds where it is more widely applied (Echevarria et al ., 2008; Gould et al ., 2009). Any tag effect detected in the arena might then correlate with movement and activity in nature (Fraser et al ., 2001; Watz, 2019; Závorka et al ., 2016), and hence constitute a warning signal concerning the suitability of the tagging method.…”

“…In fish, individual open‐field test scores have correlated with activity (Závorka et al ., 2016) and movement (Fraser et al ., 2001; Watz, 2019) in nature, as well as passage behaviour at a hydropower dam (Haraldstad et al ., 2021). Outside of ecology, it is also used to test for chemically induced alterations in animal behaviour (Echevarria et al ., 2008; Gould et al ., 2009; Hong & Zha, 2019). In this study, we apply an open‐field test in combination with a provoked swimming test to test for behavioural differences between tagged and control fish.…”