PhD Scientific Days 2023

Budapest, 22-23 June 2023

Pharmaceutical Sciences I.

The effects of tramadol on sleep structure of rats for a consecutive passive and active phase

Dóra Pothorszki1, Szabolcs Koncz1, Noémi Papp1, György Bagdy1,2
1 Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary
2 NAP3.0-SE Neuropsychopharmacology Research Group, Hungarian Brain Research Program, Semmelweis University, (H-1085, Üllői Street 26.,) Budapest, Hungary

Text of the abstract

Introduction
Tramadol is a weak, centrally acting opioid analgesic. It is a norepinephrine and serotonin reuptake inhibitor as well, therefore it may also have an antidepressant effect. One of the effects of monoamine reuptake inhibitor antidepressants is the inhibition of rapid eye movement (REM) sleep and the subsequent rebound (REM sleep rebound). However, the long-term effect of tramadol on sleep structure and quantitative electroencephalography (EEG) is not known.

Aims
Our aim was to investigate the effects of tramadol on sleep structure and quantitative EEG in rats 23 hours (passive and active phases) following acute administration.

Method
Male Wistar rats were equipped with EEG and neck muscle electrodes. After the regeneration period, an intraperitoneal tramadol injection of 5, 15 or 45 mg/kg was administered at the beginning of the passive phase, then EEG signal, EMG activity and motility of the animals for 23 hours.

Results
In the passive phase, we experienced a dose-dependent non-rapid eye movement (NREM) sleep and REM sleep inhibitory effect of tramadol, which was followed by a rebound effect in the active phase. The quantitative EEG measurement showed a dose-dependent delta and gamma power increasing effect of tramadol in the passive phase during NREM sleep. These effects were no longer observable in the active phase.

Conclusion
The REM sleep inhibitory and delta and gamma power increasing effects of tramadol in the passive phase are consistent with the effects of conventional antidepressant drugs, which confirms its potential antidepressive effect. The rebound of lost REM sleep in the active phase can be an important observation for determining the ideal time of administration. Furthermore, our study suggests that the effects on vigilance must be taken into account during tramadol therapy.

Funding
Grant: 2017-1.2.1-NKP-2017-00002, NAP2022-I-4/2022, 2020-4.1.1.-TKP2020, TKP2021-EGA-25.
The contribution of Szabolcs Koncz was supported by the ÚNKP-22-4-I-SE-26 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.