Online First 2023-09-19

Rationale: MK-801 (dizocilpine) is a non-competitive NMDA receptor antagonist originally explored for anticonvulsant potential. Despite its original purpose, its amnestic properties led to the development of pivotal models of various cognitive impairments widely employed in research and greatly impacting scientific progress. MK-801 offers several advantages; however, it also presents drawbacks, including inducing dose-dependent hyperlocomotion or ambiguous effects on anxiety, which can impact the interpretation of behavioral research results. Objectives: The present review attempts to summarize and discuss the effects of MK-801 on different types of memory and cognitive functions in animal studies. Results: A plethora of behavioral research suggests that MK-801 can detrimentally impact cognitive functions. The specific effect of this compound is influenced by variables including developmental stage, gender, species, strain, and, crucially, the administered dose. Notably, when considering the undesirable effects of MK-801, doses up to 0.1 mg/kg were found not to induce stereotypy or hyperlocomotion. Conclusion: Dizocilpine continues to be of significant importance in preclinical research, facilitating the exploration of various procognitive therapeutic agents. However, given its potential undesirable effects, it is imperative to meticulously determine the appropriate dosages and conduct supplementary evaluations for any undesirable outcomes, which could complicate the interpretation of the findings.