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

• Published in: Fishes Vol. 10; no. 5; p. 229
• Main Authors: Horká, Petra, Mavrogeni, Josefina, Langová, Veronika, Horký, Pavel, Hubený, Jan, Chrtková, Ivana, Valeš, Karel, Kuchař, Martin, Horáček, Jiří
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.05.2025
• Subjects: Animal cognition; Animal models; Antipsychotics; Behavior; Behavioural responses; Central nervous system depressants; Clozapine; cognition; Cognitive ability; Communication; Comparative analysis; Design of experiments; Electric organs; Emotional behavior; Executive function; Fish; Form perception; Glutamate receptors; Glutamatergic transmission; Glutamic acid receptors (ionotropic); Gnathonemus petersii; Hallucinations; Haloperidol; Ketamine; Memory; Mental disorders; Methyl aspartate; N-Methyl-D-aspartic acid receptors; NORT; novel object recognition; Observations; Pattern recognition; Physiological aspects; Psychosis; Psychotropic drugs; Rodents; Schizophrenia; Zebrafish; Czech Republic
• ISSN: 2410-3888; 2410-3888
• DOI: 10.3390/fishes10050229

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.