[P3] Poster: Day 3

[P3-16] Rat Model of Schizophrenia: A Comparative Study of NMDA Antagonists Using the Peak Interval Task

*Veronika Rudolfová^1,2, Kristýna Malenínská^1,3, Štěpán Wenke^1,4, Anastasia Popova¹, Tereza Nekovářová^1,2 (1. National Institute of Mental Health, Topolová 748, 250 67, Klecany (Czech Republic), 2. Faculty of Science, Charles University, Department of Zoology, Viničná 7, 128 44, Prague (Czech Republic), 3. Czech Academy of Sciences, Institute of Physiology, Vídeňská 1083, 142 20, Prague (Czech Republic), 4. Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm (Sweden))

Keywords:

NMDA antagonists,peak interval,schizophrenia,animal model,rat

Schizophrenia is often accompanied by disruptions in temporal cognition, which may be linked with impairments in executive functioning and sensory integration. These deficits can be pharmacologically modeled in rodents using NMDA receptor antagonists. In this study, we focused on interval timing using the peak interval (PI) procedure with a 15-second target duration. We trained 24 adult male Long-Evans rats in this task and after completing an extensive learning phase, animals received acute intraperitoneal injections of saline, MK-801 (0.12 mg/kg), PCP (5 mg/kg), or ketamine (10 mg/kg) in a balanced square design over four weeks. While all three antagonists target NMDA receptors, their effect on the behaviour of the tested animals significantly diverged. Linear mixed-effect models revealed that (1) MK-801 significantly increased the peak time (p = 0.004) - the mean peak time increased from 15.9 s (saline) to 22.0 s after the administration of MK-801, (2) both MK-801 (p < 0.001) and PCP (p = 0.012) led to reduced overall response rates in the task. In contrast, ketamine did not produce measurable differences from saline. Interestingly, the shape of the response curve revealed subtle differences between the substances (Kruskal-Wallis test of the kurtosis of the distribution of the lever presses: H(3) = 7.89, p = 0.048), which calls for further investigation. Our results suggest the PI procedure is a promising tool for assessing schizophrenia-related timing alterations and highlight distinct effects of different NMDA antagonists on temporal processing. The results of our study also suggest that other phenomena, such as impulsivity and addiction may play a role in operant conditioning tasks.
This study was supported by a research grant AZV NU22-04-00526 provided by the Ministry of Health, Czech Republic.