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Effects of Clozapine, Haloperidol, and the NMDA Antagonist Ketamine on Novel Object Recognition in Gnathonemus petersii: A New Possible Model for Schizophrenia Research

Petra Horká, Josefina Mavrogeni, Veronika Langová, Pavel Horký, Jan Hubený, Ivana Chrtková, Karel Valeš, Martin Kuchař, Jiřı́ Horáček

Fishes May 15, 2025 DOI: 10.3390/fishes10050229 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Experimental study Peer reviewed
Population Weakly electric fish Gnathonemus petersii
Interventions Ketamine Clozapine Haloperidol
Topics Ketamine Esketamine
Keywords Clozapine Nmda receptor Haloperidol Schizophrenia object-oriented programming Antagonist Pharmacology Dopamine
Citations 1
Key findings Ketamine combined with clozapine disrupted object recognition in Gnathonemus petersii, eliminating the preference for familiar objects.

Abstract

In animal models, ketamine, a non-competitive N-methyl-D-aspartate (NMDA) antagonist, induces schizophrenia-like symptoms, such as positive and negative symptoms, as well as cognitive deficits. In the present study, we evaluated the behavioral responses and the number of EODs (electric organ discharges) of the weakly electric fish Gnathonemus petersii using the novel object recognition task (NORT). We aimed to investigate whether pharmacological modulation of the glutamatergic system would impair cognitive functions by administering the NMDA receptor antagonist ketamine, and whether these impairments could be suppressed by the administration of typical (first-generation) and atypical (second-generation) antipsychotics—clozapine and haloperidol, respectively. G. petersii preferred the familiar object over the novel object in the NORT paradigm. Although no significant differences were observed when exploring the two identical objects during the training session, the fish spent less time, moved a shorter distance, and emitted fewer EODs in the testing phase with the novel object. No direct relationship was detected between the EODs and behavioral responses to the administration of ketamine and typical antipsychotics. Ketamine administered with atypical antipsychotic clozapine disrupted the perception of the original object, where one of the objects was preferred. In the novel object trial, the time spent on the original and new objects was attenuated to the same level.

Comparable studies

Other experimental studies on ketamine, most cited first.

Study Year Design Participants
Ketamine activates psychosis and alters limbic blood flow in schizophrenia Schizophrenic individuals 1995 Experimental study
The spectral exponent of the resting EEG indexes the presence of consciousness during unresponsiveness induced by propofol, xenon, and ketamine Healthy participants 2019 Controlled experimental study n = 15
Ketamine Increases Human Motor Cortex Excitability to Transcranial Magnetic Stimulation Normal human subjects 2003 Experimental study n = 7
Evidence that Subanesthetic Doses of Ketamine Cause Sustained Disruptions of NMDA and AMPA-Mediated Frontoparietal Connectivity in Humans Human participants 2015 Experimental study
Simultaneous population pharmacokinetic modelling of ketamine and three major metabolites in patients with treatment‐resistant bipolar depression Patients with treatment-resistant bipolar depression 2012 Population pharmacokinetic analysis n = 9

Citations in the library

Cites 5

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Ketamine Esketamine