PhD Scientific Days 2025

Pharmaceutical Sciences and Health Technologies IV.

The Disruption of Sleep-Wake Stability by Different Central Nervous System-Acting Compounds

Name of the presenter

Pothorszki Dóra

Institute/workplace of the presenter

Semmelweis University - Department of Pharmacodynamics

Authors

Dóra Pothorszki¹, Szabolcs Koncz¹, Noémi Papp¹, György Bagdy¹

1: Semmelweis University - Department of Pharmacodynamics

Text of the abstract

The treatments of central nervous system (CNS) disorders are frequently associated with alterations in the quantity and quality of the sleep-wake cycle. The most common changes involve the amount and latency of rapid-eye movement (REM) and non-REM sleep. However, to better understand how CNS-related medications influence sleep, additional parameters, such as sleep fragmentation and the frequency of transitions between stages should be evaluated.
The aim of this study was to investigate how selected CNS-active compounds, (S)-ketamine, (R)-ketamine, tramadol, and pregabalin affect sleep and wake quality, beyond conventional indicators. We introduced a parameter called sleep-wake stability, to summarize changes in the frequency of transitions between vigilance states over time.
Male Wistar rats were implanted with EEG and neck muscle EMG electrodes. After recovery, intraperitoneal injections of (S)-ketamine, (R)-ketamine (7.5, 15, or 30 mg/kg), tramadol, pregabalin (5, 15, or 45 mg/kg) or vehicle were administered at the start of the passive phase. EEG, EMG, and locomotor activity were recorded for 11 hours post-injection, and transitions between sleep-wake stages were analyzed.
All compounds affected sleep-wake stability in a dose-dependent manner. (S)- and the highest dose of (R)-ketamine reduced sleep-wake transitions, primarily due to their sustained wakefulness-enhancing effect. Tramadol increased the number of all types of transitions, while pregabalin mostly altered only REM-related transitions.
The results suggest that various CNS-active drugs can alter the stability of sleep-wake architecture, emphasizing the need to include additional parameters when assessing their effects. Further research is needed to uncover the mechanisms behind these alterations and their relevance to clinical use.
Funding:
Grant: 2017-1.2.1-NKP-2017-00002, NAP2022-I-4/2022, 2020-4.1.1.-TKP2020, TKP2021-EGA-25, 2018-1.3.1-VKE-2018-00030
The contribution of Dóra Pothorszki was supported by the EKÖP-2024-222 New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development, and Innovation Fund. The publication was prepared also with the support of the Richter Gedeon Talentum Foundation established by Richter Gedeon Plc. in concordance with the framework of the Richter Gedeon PhD Scholarship received by Dóra Pothorszki.