MK-801 increases locomotor activity in a context-dependent manner in zebrafish

How do zebrafish respond to MK-801 and amphetamine? Relevance for assessing schizophrenia-relevant endophenotypes in alternative model organisms

“…Contrary to our findings, some studies demonstrated that MK-801 exposure induced hyperlocomotion in adult zebrafish (Franscescon et al, 2020;Menezes et al, 2015), however such protocols lacked the baseline period and animals were directly placed in the test apparatus only after drug exposure. The differences in context novelty may underly the conflicting results, as suggested by a previous study by Tran et al (2016).…”

“…The exposure time and concentration curves were based in the literature (Kyzar et al, 2013;Tran et al, 2016;Zimmermann et al, 2016) and pilot studies from our group. The animals were allocated to the experimental groups following block randomization procedures to counterbalance the sex, the two different home tanks, and the test arenas between the groups.…”

“…In mice and rats, MK-801 causes hyperlocomotion, stereotypic behavior, decreased social interaction, sensorimotor gating deficits, and cognitive impairment (Jones et al, 2011). In zebrafish, a few studies have shown that MK-801 exposure causes hyperlocomotion (Franscescon et al, 2020;Menezes et al, 2015;Tran et al, 2016), social deficits (Zimmermann et al, 2016), and cognitive impairment (Cognato et al, 2012;Franscescon et al, 2020;Gaspary et al, 2018). The behavioral effects of AMPH administration, on the other hand, only recapitulate the positive symptoms of schizophrenia, which include delusions, hallucinations and agitation in humans (Krystal et al, 2005), and stereotypic behavior and hyperlocomotion in rodents (Featherstone et al, 2007;Tenn et al, 2005).…”

“…µM MK-801 caused hyperlocomotion in the social interaction test, even though this drug was devoid of effects on the total distance traveled in the locomotor tests discussed earlier. This suggests that not only context novelty(Tran et al, 2016), but also the presence of social cues can differentially modulate the effects of MK-801. This idea, however, remains to be tested in experiments that isolate both variables.…”

A critical review of zebrafish schizophrenia models: Time for validation?

“…dpf-days post-fertilization; PPI-prepulse inhibition; SCZ -Schizophrenia/schizophrenic; ypf-years post-fertilization. decreased under both light and dark conditions in 7 dpf AB strain zebrafish larvae decreased in 7 dpf TU strain larvae, but increase in 7 dpf AB strain larvae increased in 60 dpf, 120 dpf and 2 ypf zebrafish, but no effect in 30 dpf zebrafish (Menezes et al, 2015) increased in adult zebrafish decreased in the number of line crossings as a measure of general swimming activity (Swain et al, 2004) no effect on the total distance travelled during the 30-min exposure, but increase in locomotor activity after subsequent introduction to novel environment in adult AB strain zebrafish (Tran et al, 2016) perturbed PPI, stereotype, locomotion and ataxia, spatial learning impairments, motor and social behaviour disturbances (Manahan-Vaughan et al, 2008) preclinical use only; similar pharmacological properties as other NMDA receptor antagonists, e.g. ketamine (de as well as the fact that antipsychotic drugs reverse MK-801-induced behavioural changes in animals (Paine and Carlezon, 2009; resulted in MK-801 being regarded as a valuable preclinical model of schizophrenia (see columns on the left) circling behaviour + increased circling behaviour in adult zebrafish (Echevarria et al, 2008;Sison and Gerlai, 2011a,b;Swain et al, 2004) aggression − decreased aggressive behaviour in mirror test (Zimmermann et al, 2016) social withdrawal + social interaction deficits expressed as decreased shoaling behaviour (Echevarria et al, 2008;Sison and Gerlai, 2011a,b;Zimmermann et al, 2016) memory deficits + +/0 + 0 + impaired memory acquisition and consolidation in the Ymaze test (Cognato et al, 2012) impaired memory consolidation and recall but not memory acquisition in the conspecific reinforced visual discrimination plus maze (Sison and Gerlai, 2011a,b) no object preference in the novel object recognition and object location tasks in adult zebrafish…”