PUBLICATION
Acute MK-801 induces hyperactivity and changes spatio-temporal exploratory dynamics without disrupting homebase retention in zebrafish
- Authors
- Mohammed, K.A., Borba, J.V., Resmim, C.M., Pretzel, C.W., Kalueff, A.V., Canzian, J., Fontana, B.D., Rosemberg, D.B.
- ID
- ZDB-PUB-250805-11
- Date
- 2025
- Source
- Behavioural brain research : 115767 (Journal)
- Registered Authors
- Kalueff, Allan V.
- Keywords
- cognitive processes, dizocilpine, exploratory dynamics, homebase, memory consolidation, open field test
- MeSH Terms
-
- Animals
- Behavior, Animal*/drug effects
- Disease Models, Animal
- Dizocilpine Maleate*/administration & dosage
- Dizocilpine Maleate*/pharmacology
- Excitatory Amino Acid Antagonists*/administration & dosage
- Excitatory Amino Acid Antagonists*/pharmacology
- Exploratory Behavior*/drug effects
- Hyperkinesis*/chemically induced
- Male
- Open Field Test
- Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors
- Stereotyped Behavior/drug effects
- Zebrafish
- PubMed
- 40759306 Full text @ Behav. Brain Res.
Citation
Mohammed, K.A., Borba, J.V., Resmim, C.M., Pretzel, C.W., Kalueff, A.V., Canzian, J., Fontana, B.D., Rosemberg, D.B. (2025) Acute MK-801 induces hyperactivity and changes spatio-temporal exploratory dynamics without disrupting homebase retention in zebrafish. Behavioural brain research. :115767.
Abstract
The N-methyl-D-aspartate receptor (NMDAR) antagonist dizocilpine (MK-801) modulates locomotor functions and disrupts cognitive and spatial processes, making it useful for examining pharmacologically-induced behavioral phenotypes that mimic those found in schizophrenia. Here, we investigate the impact of MK-801 on spatio-temporal exploratory dynamics in zebrafish, particularly in the context of homebase behavior, using the open field test (OFT). In Experiment 1, zebrafish received (i.p.) injection of saline (0.9% NaCl) or MK-801 (2.0mg/kg), followed by a 15-min absorption period, then a 30-min OFT. Experiment 2 involved an initial 30-min OFT, immediate saline or MK-801 (2.0mg/kg, i.p.) administration, and a retrial OFT 24h later. In Experiment 1, MK-801 induced hyperactivity and stereotypy. Although zebrafish were able to establish a homebase as a functionally relevant spatial reference, notable alterations in homebase-related behaviors were observed. Experiment 2 explored the homebase conservation across repeated OFT sessions, revealing that despite subtle changes in overall exploration and homebase occupancy, both groups demonstrated significant homebase conservation and reduced thigmotaxis in the retrial. An inhibitory avoidance task (IAT) was also performed to confirm the amnesic effects of MK-801 on zebrafish (Experiment 3), revealing that MK-801 impaired aversive memory consolidation. Our novel findings indicate that, while MK-801 altered movement patterns and disrupted aversive memory, zebrafish core spatial behaviors remained intact, highlighting the adaptive value of homebase as a conserved spatial strategy. Collectively, this work further supports the utility of zebrafish models for studying how pharmacological modulations of NMDAR affect spatial orientation and exploratory behavior with translational relevance in neuropsychiatric diseases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping