Antipsychotic drugs reverse MK-801-induced cognitive and social interaction deficits in zebrafish (Danio rerio)

Zebrafish: a novel model in neuropsychopharmacological research

“…Hence, MK-801-treated zebrafish showed some behavioural features witnessed in schizophrenia, such as cognitive and social interaction deficits, which were reverted by current available atypical drugs. 19 Additionally, these same investigators categorized the behavioural effects of MK-801 and investigated the effect of typical and atypical antipsychotic treatments on locomotors activity as well on the hyper locomotion induced by MK-801 in zebrafish. MK-801 (20 microM) increased the locomotors behaviour as measured by the amount of line crossings, distance travelled, and the mean speed in the tank test after 15, 30, and 60 minutes of exposure.…”

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

“…A prime example in the rodent literature is the dose-dependent increase of locomotor activity following administration of [5R,10S-[+]-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801 or dizocilpine), a non-competitive antagonist of the N-methyl-d-aspartate receptor (NMDA-R) [3,4]. The NMDA receptor is a glutamate and glycine activated excitatory ionotropic receptor expressed in the vertebrate central nervous system (for a review see [6,7] or endophenotypes of schizophrenia in animal models-including decreased prepulse inhibition [8] as well as impairment of social behavior [9]. In addition, exposure to MK-801 has been found to have anxiolytic/antidepressant [10] as well as locomotor stimulant effects [3,4,11].…”

“…In addition, exposure to MK-801 has been found to have anxiolytic/antidepressant [10] as well as locomotor stimulant effects [3,4,11]. Recently, the effects of MK-801 have also started to be examined using zebrafish [9,[12][13][14]. The high nucleotide sequence homology of the zebrafish genome relative to the human genome offers translational relevance of the former species.…”

“…Several studies measured locomotor activity of zebrafish during exposure to the drug [12,14,19]. In other studies, zebrafish were pre-treated with MK-801 (often in a small volume exposure chamber), and the total distance traveled was quantified subsequently when the zebrafish was placed in a larger novel tank or testing apparatus without continual administration of the drug [9,13,17,18]. In the current study, we investigate whether the inconsistent reports on the effects of MK-801 on locomotor activity are potentially due to such context-dependent variables.…”

Zebrafish as a Model to Study Autism Spectrum Disorder Caused by Environmental Chemicals Exposure

“…This model is widely considered to offer numerous logistical and economic advantages over mammalian models as zebrafish spawn overnight, hatch in 2-3 days post fertilization, develop complex behavior within the first week of life, and reach sexual maturity in 2-3 months [19]. Zebrafish have been proposed as a model of Alzheimer´s disease [20,21], schizophrenia [22], drug abuse [23], and other brain disorders [24,25]. The utility of both adult and larval zebrafish in neuroscience has grown markedly in the past decades because it is a vertebrate species with high physiological and genetic homology to humans (69% of zebrafish genes have human orthologs meaning that it is frequently possible to study human disease-related genes in fish), and also because of the ease of genetic manipulation, fully characterized genome [24,[26][27][28][29][30][31].…”